Multiple Sclerosis and T Lymphocytes: An Entangled Story (original) (raw)

References

• Abrahamsson SV, Angelini DF, Dubinsky AN, Morel E, Oh U, Jones JL, Carassiti D, Reynolds R, Salvetti M, Calabresi PA, Coles AJ, Battistini L, Martin R, Burt RK, Muraro PA (2013) Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain 136:2888–2903
  Article PubMed Central PubMed Google Scholar
• Allegretta M, Nicklas JA, Sriram S, Albertini RJ (1990) T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247:718–721
  Article CAS PubMed Google Scholar
• Almolda B, Gonzalez B, Castellano B (2010) Activated microglial cells acquire an immature dendritic cell phenotype and may terminate the immune response in an acute model of EAE. J Neuroimmunol 223:39–54
  Article CAS PubMed Google Scholar
• Almolda B, Gonzalez B, Castellano B (2011) Antigen presentation in EAE: role of microglia, macrophages and dendritic cells. Front Biosci (Landmark Ed) 16:1157–1171
  Article CAS Google Scholar
• Aloisi F, Penna G, Polazzi E, Minghetti L, Adorini L (1999) CD40-CD154 interaction and IFN-gamma are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Th1 cells. J Immunol 162:1384–1391
  CAS PubMed Google Scholar
• Anderton SM, Kissler S, Lamont AG, Wraith DC (1999) Therapeutic potential of TCR antagonists is determined by their ability to modulate a diverse repertoire of autoreactive T cells. Eur J Immunol 29:1850–1857
  Article CAS PubMed Google Scholar
• Annibali V, Ristori G, Angelini DF, Serafini B, Mechelli R, Cannoni S, Romano S, Paolillo A, Abderrahim H, Diamantini A, Borsellino G, Aloisi F, Battistini L, Salvetti M (2011) CD161(high)CD8 + T cells bear pathogenetic potential in multiple sclerosis. Brain 134:542–554
  Article PubMed Google Scholar
• Antel JP, Bania MB, Reder A, Cashman N (1986) Activated suppressor cell dysfunction in progressive multiple sclerosis. J Immunol 137:137–141
  CAS PubMed Google Scholar
• Antel J, Brown M, Nicholas MK, Blain M, Noronha A, Reder A (1988) Activated suppressor cell function in multiple sclerosis–clinical correlations. J Neuroimmunol 17:323–330
  Article CAS PubMed Google Scholar
• Astier AL, Meiffren G, Freeman S, Hafler DA (2006) Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin Invest 116:3252–3257
  Article PubMed Central CAS PubMed Google Scholar
• Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341
  Article PubMed Central CAS PubMed Google Scholar
• Atarashi K et al (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500:232–236
  Article CAS PubMed Google Scholar
• Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL (2007) A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8:1380–1389
  Article CAS PubMed Google Scholar
• Axtell RC, de Jong BA, Boniface K, van der Voort LF, Bhat R, De Sarno P, Naves R, Han M, Zhong F, Castellanos JG, Mair R, Christakos A, Kolkowitz I, Katz L, Killestein J, Polman CH, de Waal MR, Steinman L, Raman C (2010) T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med 16:406–412
  Article PubMed Central CAS PubMed Google Scholar
• Axtell RC, Raman C, Steinman L (2013) Type I interferons: beneficial in Th1 and detrimental in Th17 autoimmunity. Clin Rev Allergy Immunol 44:114–120
  Article CAS PubMed Google Scholar
• Babbe H, Roers A, Waisman A, Lassmann H, Goebels N, Hohlfeld R, Friese M, Schroder R, Deckert M, Schmidt S, Ravid R, Rajewsky K (2000) Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med 192:393–404
  Article PubMed Central CAS PubMed Google Scholar
• Baecher-Allan CM, Costantino CM, Cvetanovich GL, Ashley CW, Beriou G, Dominguez-Villar M, Hafler DA (2011) CD2 costimulation reveals defective activity by human CD4 + CD25(hi) regulatory cells in patients with multiple sclerosis. J Immunol 186:3317–3326
  Article PubMed Central CAS PubMed Google Scholar
• Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, de Waal-Malefyt R, Coffman RL, Hawrylowicz CM, O’Garra A (2002) In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 195:603–616
  Article PubMed Central CAS PubMed Google Scholar
• Bartholomaus I, Kawakami N, Odoardi F, Schlager C, Miljkovic D, Ellwart JW, Klinkert WE, Flugel-Koch C, Issekutz TB, Wekerle H, Flugel A (2009) Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462:94–98
  Article PubMed CAS Google Scholar
• Baughman EJ, Mendoza JP, Ortega SB, Ayers CL, Greenberg BM, Frohman EM, Karandikar NJ (2011) Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis. J Autoimmun 36:115–124
  Article PubMed Central CAS PubMed Google Scholar
• Baxter AG (2007) The origin and application of experimental autoimmune encephalomyelitis. Nat Rev Immunol 7:904–912
  Article CAS PubMed Google Scholar
• Behrens F, Tak PP, Ostergaard M, Stoilov R, Wiland P, Huizinga TW, Berenfus VY, Vladeva S, Rech J, Rubbert-Roth A, Korkosz M, Rekalov D, Zupanets IA, Ejbjerg BJ, Geiseler J, Fresenius J, Korolkiewicz RP, Schottelius AJ, Burkhardt H (2014) MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis. doi:10.1136/annrheumdis-2013-204816
  PubMed Central PubMed Google Scholar
• Berer K, Krishnamoorthy G (2014) Microbial view of central nervous system autoimmunity. FEBS Lett 588:4207–4213
  Article CAS PubMed Google Scholar
• Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G (2011) Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479:538–541
  Article CAS PubMed Google Scholar
• Berthelot L, Laplaud DA, Pettre S, Ballet C, Michel L, Hillion S, Braudeau C, Connan F, Lefrere F, Wiertlewski S, Guillet JG, Brouard S, Choppin J, Soulillou JP (2008) Blood CD8+ T cell responses against myelin determinants in multiple sclerosis and healthy individuals. Eur J Immunol 38:1889–1899
  Article CAS PubMed Google Scholar
• Bhargava P, Mowry EM (2014) Gut microbiome and multiple sclerosis. Curr Neurol Neurosci Rep 14:492
  Article PubMed CAS Google Scholar
• Bielekova B, Goodwin B, Richert N, Cortese I, Kondo T, Afshar G, Gran B, Eaton J, Antel J, Frank JA, McFarland HF, Martin R (2000) Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 6:1167–1175
  Article CAS PubMed Google Scholar
• Bielekova B, Sung MH, Kadom N, Simon R, McFarland H, Martin R (2004) Expansion and functional relevance of high-avidity myelin-specific CD4+ T cells in multiple sclerosis. J Immunol 172:3893–3904
  Article CAS PubMed Google Scholar
• Bin Dhuban K, d’Hennezel E, Nashi E, Bar-Or A, Rieder S, Shevach EM, Nagata S, Piccirillo CA (2015) Coexpression of TIGIT and FCRL3 Identifies Helios + Human Memory Regulatory T Cells. J Immunol 194:3687–3696
  Article CAS PubMed Google Scholar
• Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Bruck W (2000) Acute axonal injury in multiple sclerosis. correlation with demyelination and inflammation. Brain 123:1174–1183
  Article PubMed Google Scholar
• Bokori-Brown M, Savva CG, Fernandes da Costa SP, Naylor CE, Basak AK, Titball RW (2011) Molecular basis of toxicity of Clostridium perfringens epsilon toxin. FEBS J 278:4589–4601
  Article CAS PubMed Google Scholar
• Brynedal B, Duvefelt K, Jonasdottir G, Roos IM, Akesson E, Palmgren J, Hillert J (2007) HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis. PLoS ONE 2:e664
  Article PubMed Central PubMed CAS Google Scholar
• Calzascia T, Masson F, Di Berardino-Besson W, Contassot E, Wilmotte R, Aurrand-Lions M, Ruegg C, Dietrich PY, Walker PR (2005) Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs. Immunity 22:175–184
  Article CAS PubMed Google Scholar
• Carrieri PB, Provitera V, De Rosa T, Tartaglia G, Gorga F, Perrella O (1998) Profile of cerebrospinal fluid and serum cytokines in patients with relapsing-remitting multiple sclerosis: a correlation with clinical activity. Immunopharmacol Immunotoxicol 20:373–382
  Article CAS PubMed Google Scholar
• Carson MJ, Sutcliffe JG, Campbell IL (1999) Microglia stimulate naive T-cell differentiation without stimulating T-cell proliferation. J Neurosci Res 55:127–134
  Article CAS PubMed Google Scholar
• Cayrol R, Wosik K, Berard JL, Dodelet-Devillers A, Ifergan I, Kebir H, Haqqani AS, Kreymborg K, Krug S, Moumdjian R, Bouthillier A, Becher B, Arbour N, David S, Stanimirovic D, Prat A (2008) Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol 9:137–145
  Article CAS PubMed Google Scholar
• Chastain EM, Miller SD (2012) Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. Immunol Rev 245:227–238
  Article PubMed Central CAS PubMed Google Scholar
• Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hunter CA, Kastelein RA, Cua DJ (2006) Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 116:1317–1326
  Article PubMed Central CAS PubMed Google Scholar
• Cheng W, Chen G (2014) Chemokines and chemokine receptors in multiple sclerosis. Mediators Inflamm 2014:659206
  PubMed Central PubMed Google Scholar
• Chiarini M, Serana F, Zanotti C, Capra R, Rasia S, Rottoli M, Rovaris M, Caputo D, Cavaletti G, Frigo M, Frigeni B, Clerici R, Rezzonico M, Caimi L, Imberti L (2012) Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy. Mult Scler 18:788–798
  Article CAS PubMed Google Scholar
• Chou YK, Bourdette DN, Offner H, Whitham R, Wang RY, Hashim GA, Vandenbark AA (1992) Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis. J Neuroimmunol 38:105–113
  Article CAS PubMed Google Scholar
• Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, Suter T, Becher B (2011) RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 12:560–567
  Article CAS PubMed Google Scholar
• Codarri L, Greter M, Becher B (2013) Communication between pathogenic T cells and myeloid cells in neuroinflammatory disease. Trends Immunol 34:114–119
  Article CAS PubMed Google Scholar
• Correale J, Farez M (2007) Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 61:97–108
  Article CAS PubMed Google Scholar
• Correale J, Farez MF (2011) The impact of parasite infections on the course of multiple sclerosis. J Neuroimmunol 233:6–11
  Article CAS PubMed Google Scholar
• Correale J, Villa A (2008) Isolation and characterization of CD8+ regulatory T cells in multiple sclerosis. J Neuroimmunol 195:121–134
  Article CAS PubMed Google Scholar
• Crawford MP, Yan SX, Ortega SB, Mehta RS, Hewitt RE, Price DA, Stastny P, Douek DC, Koup RA, Racke MK, Karandikar NJ (2004) High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood 103:4222–4231
  Article CAS PubMed Google Scholar
• Cross AH, Naismith RT (2014) Established and novel disease-modifying treatments in multiple sclerosis. J Intern Med 275:350–363
  Article CAS PubMed Google Scholar
• Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748
  Article CAS PubMed Google Scholar
• Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K (2012) Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 3:1227
  Article PubMed Central PubMed CAS Google Scholar
• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505:559–563
  Article PubMed Central CAS PubMed Google Scholar
• de Andres C, Aristimuno C, de Las HV, Martinez-Gines ML, Bartolome M, Arroyo R, Navarro J, Gimenez-Roldan S, Fernandez-Cruz E, Sanchez-Ramon S (2007) Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: an ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis. J Neuroimmunol 182:204–211
  Article PubMed CAS Google Scholar
• de Vos AF, van Meurs M, Brok HP, Boven LA, Hintzen RQ, van der Valk P, Ravid R, Rensing S, Boon L, t Hart BA, Laman JD (2002) Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol 169:5415–5423
  Article PubMed Google Scholar
• Ding Q, Lu L, Wang B, Zhou Y, Jiang Y, Zhou X, Xin L, Jiao Z, Chou KY (2006) B7H1-Ig fusion protein activates the CD4+ IFN-gamma receptor + type 1 T regulatory subset through IFN-gamma-secreting Th1 cells. J Immunol 177:3606–3614
  Article CAS PubMed Google Scholar
• Duan H, Xing S, Luo Y, Feng L, Gramaglia I, Zhang Y, Lu D, Zeng Q, Fan K, Feng J, Yang D, Qin Z, Couraud PO, Romero IA, Weksler B, Yan X (2013) Targeting endothelial CD146 attenuates neuroinflammation by limiting lymphocyte extravasation to the CNS. Sci Rep 3:1687
  PubMed Central PubMed Google Scholar
• Durafourt BA, Moore CS, Zammit DA, Johnson TA, Zaguia F, Guiot MC, Bar-Or A, Antel JP (2012) Comparison of polarization properties of human adult microglia and blood-derived macrophages. Glia 60:717–727
  Article PubMed Google Scholar
• Dusseaux M, Martin E, Serriari N, Peguillet I, Premel V, Louis D, Milder M, Le Bourhis L, Soudais C, Treiner E, Lantz O (2011) Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117:1250–1259
  Article CAS PubMed Google Scholar
• Ebner F, Brandt C, Thiele P, Richter D, Schliesser U, Siffrin V, Schueler J, Stubbe T, Ellinghaus A, Meisel C, Sawitzki B, Nitsch R (2013) Microglial activation milieu controls regulatory T cell responses. J Immunol 191:5594–5602
  Article CAS PubMed Google Scholar
• El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, Zhang GX, Dittel BN, Rostami A (2011) The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 12:568–575
  Article PubMed Central CAS PubMed Google Scholar
• Elhofy A, Depaolo RW, Lira SA, Lukacs NW, Karpus WJ (2009) Mice deficient for CCR6 fail to control chronic experimental autoimmune encephalomyelitis. J Neuroimmunol 213:91–99
  Article PubMed Central CAS PubMed Google Scholar
• Elong Ngono A, Pettre S, Salou M, Bahbouhi B, Soulillou JP, Brouard S, Laplaud DA (2012) Frequency of circulating autoreactive T cells committed to myelin determinants in relapsing-remitting multiple sclerosis patients. Clin Immunol 144:117–126
  Article CAS PubMed Google Scholar
• Engelhardt B, Ransohoff RM (2012) Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol 33:579–589
  Article CAS PubMed Google Scholar
• Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, Dalton D, Fathman CG (1996) Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 156:5–7
  CAS PubMed Google Scholar
• Fitzgerald DC, Zhang GX, El-Behi M, Fonseca-Kelly Z, Li H, Yu S, Saris CJ, Gran B, Ciric B, Rostami A (2007) Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 8:1372–1379
  Article CAS PubMed Google Scholar
• Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH (2010) T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 162:1–11
  Article PubMed Central CAS PubMed Google Scholar
• Fogdell-Hahn A, Ligers A, Gronning M, Hillert J, Olerup O (2000) Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens 55:140–148
  Article CAS PubMed Google Scholar
• Friese MA, Fugger L (2005) Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain 128:1747–1763
  Article PubMed Google Scholar
• Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H (2009) The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 132:1175–1189
  Article PubMed Central PubMed Google Scholar
• Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis–the plaque and its pathogenesis. N Engl J Med 354:942–955
  Article CAS PubMed Google Scholar
• Fugger L, Friese MA, Bell JI (2009) From genes to function: the next challenge to understanding multiple sclerosis. Nat Rev Immunol 9:408–417
  Article CAS PubMed Google Scholar
• Fujinami RS, Oldstone MB (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230:1043–1045
  Article CAS PubMed Google Scholar
• Gapin L (2014) Check MAIT. J Immunol 192:4475–4480
  Article PubMed Central CAS PubMed Google Scholar
• Gartner D, Hoff H, Gimsa U, Burmester GR, Brunner-Weinzierl MC (2006) CD25 regulatory T cells determine secondary but not primary remission in EAE: impact on long-term disease progression. J Neuroimmunol 172:73–84
  Article PubMed CAS Google Scholar
• Gaur A, Boehme SA, Chalmers D, Crowe PD, Pahuja A, Ling N, Brocke S, Steinman L, Conlon PJ (1997) Amelioration of relapsing experimental autoimmune encephalomyelitis with altered myelin basic protein peptides involves different cellular mechanisms. J Neuroimmunol 74:149–158
  Article CAS PubMed Google Scholar
• Gay FW, Drye TJ, Dick GW, Esiri MM (1997) The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. identification and characterization of the primary demyelinating lesion. Brain 120:1461–1483
  Article PubMed Google Scholar
• Geginat J, Paroni M, Maglie S, Alfen JS, Kastirr I, Gruarin P, De Simone M, Pagani M, Abrignani S (2014) Plasticity of human CD4 T cell subsets. Front Immunol 5:630
  Article PubMed Central PubMed CAS Google Scholar
• Genain CP, Zamvil SS (2000) Specific immunotherapy: one size does not fit all. Nat Med 6:1098–1100
  Article CAS PubMed Google Scholar
• Giannetti P, Politis M, Su P, Turkheimer FE, Malik O, Keihaninejad S, Wu K, Waldman A, Reynolds R, Nicholas R, Piccini P (2015) Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome. Brain 138:110–119
  Article PubMed PubMed Central Google Scholar
• Giunti D, Parodi B, Cordano C, Uccelli A, Kerlero de Rosbo N (2014) Can we switch microglia’s phenotype to foster neuroprotection? Focus on multiple sclerosis. Immunology 141:328–339
  Article PubMed Central CAS PubMed Google Scholar
• Gobin SJ, Montagne L, Van Zutphen M, Van Der Valk P, Van Den Elsen PJ, De Groot CJ (2001) Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions. Glia 36:68–77
  Article CAS PubMed Google Scholar
• Goldmann T, Prinz M (2013) Role of microglia in CNS autoimmunity. Clin Dev Immunol 2013:208093
  Article PubMed Central PubMed CAS Google Scholar
• Goverman J (2009) Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 9:393–407
  Article PubMed Central CAS PubMed Google Scholar
• Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328–334
  Article CAS PubMed Google Scholar
• Griffith JW, Sokol CL, Luster AD (2014) Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol 32:659–702
  Article CAS PubMed Google Scholar
• Guo B, Chang EY, Cheng G (2008) The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J Clin Invest 118:1680–1690
  Article PubMed Central CAS PubMed Google Scholar
• Haak S, Croxford AL, Kreymborg K, Heppner FL, Pouly S, Becher B, Waisman A (2009) IL-17A and IL-17 F do not contribute vitally to autoimmune neuro-inflammation in mice. J Clin Invest 119:61–69
  PubMed Central CAS PubMed Google Scholar
• Haas J, Korporal M, Balint B, Fritzsching B, Schwarz A, Wildemann B (2009) Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. J Neuroimmunol 216:113–117
  Article CAS PubMed Google Scholar
• Harbo HF et al (2004) Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis. Tissue Antigens 63:237–247
  Article CAS PubMed Google Scholar
• Harris MG, Hulseberg P, Ling C, Karman J, Clarkson BD, Harding JS, Zhang M, Sandor A, Christensen K, Nagy A, Sandor M, Fabry Z (2014) Immune privilege of the CNS is not the consequence of limited antigen sampling. Sci Rep 4:4422
  PubMed Central PubMed Google Scholar
• Hauser SL, Bhan AK, Gilles F, Kemp M, Kerr C, Weiner HL (1986) Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol 19:578–587
  Article CAS PubMed Google Scholar
• Hemmer B, Fleckenstein BT, Vergelli M, Jung G, McFarland H, Martin R, Wiesmuller KH (1997) Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J Exp Med 185:1651–1659
  Article PubMed Central CAS PubMed Google Scholar
• Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B (2011) Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 12:255–263
  Article PubMed Central CAS PubMed Google Scholar
• Hoftberger R, Aboul-Enein F, Brueck W, Lucchinetti C, Rodriguez M, Schmidbauer M, Jellinger K, Lassmann H (2004) Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions. Brain Pathol 14:43–50
  Article CAS PubMed Google Scholar
• Howe CL, Ure D, Adelson JD, LaFrance-Corey R, Johnson A, Rodriguez M (2007) CD8+ T cells directed against a viral peptide contribute to loss of motor function by disrupting axonal transport in a viral model of fulminant demyelination. J Neuroimmunol 188:13–21
  Article PubMed Central CAS PubMed Google Scholar
• Hu D, Weiner HL, Ritz J (2013) Identification of cytolytic CD161–CD56+ regulatory CD8 T cells in human peripheral blood. PLoS One 8:e59545
  Article PubMed Central CAS PubMed Google Scholar
• Huber M, Heink S, Pagenstecher A, Reinhard K, Ritter J, Visekruna A, Guralnik A, Bollig N, Jeltsch K, Heinemann C, Wittmann E, Buch T, Prazeres da Costa O, Brustle A, Brenner D, Mak TW, Mittrucker HW, Tackenberg B, Kamradt T, Lohoff M (2013) IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. J Clin Invest 123:247–260
  Article PubMed Central CAS PubMed Google Scholar
• Hucke S, Flossdorf J, Grutzke B, Dunay IR, Frenzel K, Jungverdorben J, Linnartz B, Mack M, Peitz M, Brustle O, Kurts C, Klockgether T, Neumann H, Prinz M, Wiendl H, Knolle P, Klotz L (2012) Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor gamma. Brain 135:1586–1605
  Article PubMed Google Scholar
• Huizinga R, Hintzen RQ, Assink K, van Meurs M, Amor S (2009) T-cell responses to neurofilament light protein are part of the normal immune repertoire. Int Immunol 21:433–441
  Article CAS PubMed Google Scholar
• Huseby ES, Liggitt D, Brabb T, Schnabel B, Ohlen C, Goverman J (2001) A pathogenic role for myelin-specific cd8(+) t cells in a model for multiple sclerosis. J Exp Med 194:669–676
  Article PubMed Central CAS PubMed Google Scholar
• Ifergan I, Kebir H, Alvarez JI, Marceau G, Bernard M, Bourbonniere L, Poirier J, Duquette P, Talbot PJ, Arbour N, Prat A (2011) Central nervous system recruitment of effector memory CD8+ T lymphocytes during neuroinflammation is dependent on alpha4 integrin. Brain 134:3560–3577
  Article PubMed Google Scholar
• Jack CS, Arbour N, Manusow J, Montgrain V, Blain M, McCrea E, Shapiro A, Antel JP (2005) TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 175:4320–4330
  Article CAS PubMed Google Scholar
• Jacobsen M, Cepok S, Quak E, Happel M, Gaber R, Ziegler A, Schock S, Oertel WH, Sommer N, Hemmer B (2002) Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients. Brain 125:538–550
  Article PubMed Google Scholar
• Jadidi-Niaragh F, Mirshafiey A (2011) Regulatory T-cell as orchestra leader in immunosuppression process of multiple sclerosis. Immunopharmacol Immunotoxicol 33:545–567
  Article CAS PubMed Google Scholar
• Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK (2009) Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 183:7169–7177
  Article PubMed Central PubMed CAS Google Scholar
• Jarry U, Jeannin P, Pineau L, Donnou S, Delneste Y, Couez D (2013) Efficiently stimulated adult microglia cross-prime naive CD8(+) T cells injected in the brain. Eur J Immunol 43:1173–1184
  Article CAS PubMed Google Scholar
• Ji Q, Perchellet A, Goverman JM (2010) Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs. Nat Immunol 11:628–634
  Article PubMed Central CAS PubMed Google Scholar
• Ji Q, Castelli L, Goverman JM (2013) MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to CD8(+) T cells. Nat Immunol 14:254–261
  Article PubMed Central CAS PubMed Google Scholar
• Jiang H, Chess L (2004) An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest 114:1198–1208
  Article PubMed Central CAS PubMed Google Scholar
• Jiang H, Ware R, Stall A, Flaherty L, Chess L, Pernis B (1995) Murine CD8+ T cells that specifically delete autologous CD4+ T cells expressing V beta 8 TCR: a role of the Qa-1 molecule. Immunity 2:185–194
  Article CAS PubMed Google Scholar
• Jilek S, Schluep M, Rossetti AO, Guignard L, Le Goff G, Pantaleo G, Du Pasquier RA (2007) CSF enrichment of highly differentiated CD8+ T cells in early multiple sclerosis. Clin Immunol 123:105–113
  Article CAS PubMed Google Scholar
• Jones JL, Anderson JM, Phuah CL, Fox EJ, Selmaj K, Margolin D, Lake SL, Palmer J, Thompson SJ, Wilkins A, Webber DJ, Compston DA, Coles AJ (2010) Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain 133:2232–2247
  Article PubMed Google Scholar
• Junker A, Ivanidze J, Malotka J, Eiglmeier I, Lassmann H, Wekerle H, Meinl E, Hohlfeld R, Dornmair K (2007) Multiple sclerosis: T-cell receptor expression in distinct brain regions. Brain 130:2789–2799
  Article PubMed Google Scholar
• Jurewicz A, Biddison WE, Antel JP (1998) MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes. J Immunol 160:3056–3059
  CAS PubMed Google Scholar
• Kabat EA, Wolf A, Bezer AE, Murray JP (1951) Studies on acute disseminated encephalomyelitis produced experimentally in rhesus monkeys. J Exp Med 93:615–633
  Article PubMed Central CAS PubMed Google Scholar
• Kawamoto S, Maruya M, Kato LM, Suda W, Atarashi K, Doi Y, Tsutsui Y, Qin H, Honda K, Okada T, Hattori M, Fagarasan S (2014) Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41:152–165
  Article CAS PubMed Google Scholar
• Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A (2007) Human TH17 lymphocytes promote blood–brain barrier disruption and central nervous system inflammation. Nat Med 13:1173–1175
  Article CAS PubMed Google Scholar
• Kebir H, Ifergan I, Alvarez JI, Bernard M, Poirier J, Arbour N, Duquette P, Prat A (2009) Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann Neurol 66:390–402
  Article CAS PubMed Google Scholar
• Kivisakk P, Mahad DJ, Callahan MK, Sikora K, Trebst C, Tucky B, Wujek J, Ravid R, Staugaitis SM, Lassmann H, Ransohoff RM (2004) Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Ann Neurol 55:627–638
  Article CAS PubMed Google Scholar
• Kleinewietfeld M, Hafler DA (2014) Regulatory T cells in autoimmune neuroinflammation. Immunol Rev 259:231–244
  Article PubMed Central CAS PubMed Google Scholar
• Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA (2013) Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496:518–522
  Article PubMed Central CAS PubMed Google Scholar
• Koch MW, Metz LM, Agrawal SM, Yong VW (2013) Environmental factors and their regulation of immunity in multiple sclerosis. J Neurol Sci 324:10–16
  Article PubMed Google Scholar
• Kohm AP, Carpentier PA, Anger HA, Miller SD (2002) Cutting edge: CD4 + CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 169:4712–4716
  Article CAS PubMed Google Scholar
• Kooi EJ, van Horssen J, Witte ME, Amor S, Bo L, Dijkstra CD, van der Valk P, Geurts JJ (2009) Abundant extracellular myelin in the meninges of patients with multiple sclerosis. Neuropathol Appl Neurobiol 35:283–295
  Article CAS PubMed Google Scholar
• Korporal M, Haas J, Balint B, Fritzsching B, Schwarz A, Moeller S, Fritz B, Suri-Payer E, Wildemann B (2008) Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells. Arch Neurol 65:1434–1439
  Article PubMed Google Scholar
• Kreymborg K, Etzensperger R, Dumoutier L, Haak S, Rebollo A, Buch T, Heppner FL, Renauld JC, Becher B (2007) IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J Immunol 179:8098–8104
  Article CAS PubMed Google Scholar
• Krishnamoorthy G, Saxena A, Mars LT, Domingues HS, Mentele R, Ben-Nun A, Lassmann H, Dornmair K, Kurschus FC, Liblau RS, Wekerle H (2009) Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis. Nat Med 15:626–632
  Article CAS PubMed Google Scholar
• Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM (2008) IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med 205:1535–1541
  Article PubMed Central CAS PubMed Google Scholar
• Krumbholz M, Derfuss T, Hohlfeld R, Meinl E (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613–623
  Article CAS PubMed Google Scholar
• Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Bruck W (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202–2212
  Article PubMed Google Scholar
• Kumar N, Narang K, Cressey BD, Gottlieb AB (2013) Long-term safety of ustekinumab for psoriasis. Expert Opin Drug Saf 12:757–765
  Article CAS PubMed Google Scholar
• Laman JD, Weller RO (2013) Drainage of cells and soluble antigen from the CNS to regional lymph nodes. J Neuroimmune Pharmacol 8:840–856
  Article PubMed Google Scholar
• Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240
  Article PubMed Central CAS PubMed Google Scholar
• Larochelle C, Alvarez JI, Prat A (2011) How do immune cells overcome the blood–brain barrier in multiple sclerosis? FEBS Lett 585:3770–3780
  Article CAS PubMed Google Scholar
• Larochelle C, Cayrol R, Kebir H, Alvarez JI, Lecuyer MA, Ifergan I, Viel E, Bourbonniere L, Beauseigle D, Terouz S, Hachehouche L, Gendron S, Poirier J, Jobin C, Duquette P, Flanagan K, Yednock T, Arbour N, Prat A (2012) Melanoma cell adhesion molecule identifies encephalitogenic T lymphocytes and promotes their recruitment to the central nervous system. Brain 135:2906–2924
  Article PubMed Google Scholar
• Larochelle C, Lecuyer MA, Alvarez JI, Charabati M, Saint-Laurent O, Ghannam S, Kebir H, Flanagan K, Yednock T, Duquette P, Arbour N, Prat A (2015) MCAM CD8 T lymphocytes mediate CNS inflammation. Ann Neurol. doi:10.1002/ana.24415
  PubMed Google Scholar
• Lassmann H (2004) Recent neuropathological findings in MS–implications for diagnosis and therapy. J Neurol 251(Suppl 4):IV2–IV5
  PubMed Google Scholar
• Lassmann H (2014) Mechanisms of white matter damage in multiple sclerosis. Glia 62:1816–1830
  Article PubMed Google Scholar
• Le Bourhis L, Guerri L, Dusseaux M, Martin E, Soudais C, Lantz O (2011) Mucosal-associated invariant T cells: unconventional development and function. Trends Immunol 32:212–218
  Article PubMed CAS Google Scholar
• Lee YH, Ishida Y, Rifa’i M, Shi Z, Isobe K, Suzuki H (2008) Essential role of CD8 + CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. J Immunol 180:825–832
  Article CAS PubMed Google Scholar
• Lee YK, Menezes JS, Umesaki Y, Mazmanian SK (2011) Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 108(Suppl 1):4615–4622
  Article PubMed Central CAS PubMed Google Scholar
• Li Y, Chu N, Hu A, Gran B, Rostami A, Zhang GX (2007) Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain 130:490–501
  Article PubMed Google Scholar
• Liblau R, Tournier-Lasserve E, Maciazek J, Dumas G, Siffert O, Hashim G, Bach MA (1991) T cell response to myelin basic protein epitopes in multiple sclerosis patients and healthy subjects. Eur J Immunol 21:1391–1395
  Article CAS PubMed Google Scholar
• Lindsey JW, Hodgkinson S, Mehta R, Mitchell D, Enzmann D, Steinman L (1994) Repeated treatment with chimeric anti-CD4 antibody in multiple sclerosis. Ann Neurol 36:183–189
  Article CAS PubMed Google Scholar
• Link H (1998) The cytokine storm in multiple sclerosis. Mult Scler 4:12–15
  Article CAS PubMed Google Scholar
• Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, de St F, Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711
  Article PubMed Central CAS PubMed Google Scholar
• Llewellyn-Smith N, Lai M, Miller DH, Rudge P, Thompson AJ, Cuzner ML (1997) Effects of anti-CD4 antibody treatment on lymphocyte subsets and stimulated tumor necrosis factor alpha production: a study of 29 multiple sclerosis patients entered into a clinical trial of cM-T412. Neurology 48:810–816
  Article CAS PubMed Google Scholar
• Lovett-Racke AE, Yang Y, Racke MK (2011) Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis? Biochim Biophys Acta 1812:246–251
  Article PubMed Central CAS PubMed Google Scholar
• Lowther DE, Hafler DA (2012) Regulatory T cells in the central nervous system. Immunol Rev 248:156–169
  Article PubMed Google Scholar
• Lu L, Kim HJ, Werneck MB, Cantor H (2008) Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc Natl Acad Sci U S A 105:19420–19425
  Article PubMed Central CAS PubMed Google Scholar
• Lublin FD, Knobler RL, Kalman B, Goldhaber M, Marini J, Perrault M, D’Imperio C, Joseph J, Alkan SS, Korngold R (1993) Monoclonal anti-gamma interferon antibodies enhance experimental allergic encephalomyelitis. Autoimmunity 16:267–274
  Article CAS PubMed Google Scholar
• Lucca LE, Desbois S, Ramadan A, Ben-Nun A, Eisenstein M, Carrie N, Guery JC, Sette A, Nguyen P, Geiger TL, Mars LT, Liblau RS (2014) Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T cells in C57BL/6 mice. J Immunol 193:3267–3277
  Article CAS PubMed Google Scholar
• Lucchinetti CF, Popescu BF, Bunyan RF, Moll NM, Roemer SF, Lassmann H, Bruck W, Parisi JE, Scheithauer BW, Giannini C, Weigand SD, Mandrekar J, Ransohoff RM (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365:2188–2197
  Article PubMed Central CAS PubMed Google Scholar
• Lutterotti A, Martin R (2014) Antigen-specific tolerization approaches in multiple sclerosis. Expert Opin Investig Drugs 23:9–20
  Article CAS PubMed Google Scholar
• Major EO (2010) Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 61:35–47
  Article CAS PubMed Google Scholar
• Mars LT, Saikali P, Liblau RS, Arbour N (2011) Contribution of CD8 T lymphocytes to the immuno-pathogenesis of multiple sclerosis and its animal models. Biochim Biophys Acta 1812:151–161
  Article CAS PubMed Google Scholar
• Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, Inoges S, Lopez-Diaz de Cerio A, Palacios R, Sepulcre J, Moreno B, Gonzalez Z, Fernandez-Diez B, Melero I, Bendandi M, Villoslada P (2008) IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. Eur J Immunol 38:576–586
  Article CAS PubMed Google Scholar
• Masson F, Calzascia T, Di Berardino-Besson W, de Tribolet N, Dietrich PY, Walker PR (2007) Brain microenvironment promotes the final functional maturation of tumor-specific effector CD8+ T cells. J Immunol 179:845–853
  Article CAS PubMed Google Scholar
• Matyszak MK, Denis-Donini S, Citterio S, Longhi R, Granucci F, Ricciardi-Castagnoli P (1999) Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation. Eur J Immunol 29:3063–3076
  Article CAS PubMed Google Scholar
• Mayo L, Quintana FJ, Weiner HL (2012) The innate immune system in demyelinating disease. Immunol Rev 248:170–187
  Article PubMed Central PubMed Google Scholar
• McGeachy MJ, Stephens LA, Anderton SM (2005) Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4 + CD25+ regulatory cells within the central nervous system. J Immunol 175:3025–3032
  Article CAS PubMed Google Scholar
• McMahon EJ, Bailey SL, Castenada CV, Waldner H, Miller SD (2005) Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 11:335–339
  Article CAS PubMed Google Scholar
• McQualter JL, Darwiche R, Ewing C, Onuki M, Kay TW, Hamilton JA, Reid HH, Bernard CC (2001) Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J Exp Med 194:873–882
  Article PubMed Central CAS PubMed Google Scholar
• McRae BL, Vanderlugt CL, Dal Canto MC, Miller SD (1995) Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J Exp Med 182:75–85
  Article CAS PubMed Google Scholar
• Mellergard J, Edstrom M, Vrethem M, Ernerudh J, Dahle C (2010) Natalizumab treatment in multiple sclerosis: marked decline of chemokines and cytokines in cerebrospinal fluid. Mult Scler 16:208–217
  Article CAS PubMed Google Scholar
• Michel L, Berthelot L, Pettre S, Wiertlewski S, Lefrere F, Braudeau C, Brouard S, Soulillou JP, Laplaud DA (2008) Patients with relapsing-remitting multiple sclerosis have normal Treg function when cells expressing IL-7 receptor alpha-chain are excluded from the analysis. J Clin Invest 118:3411–3419
  PubMed Central CAS PubMed Google Scholar
• Mikita J, Dubourdieu-Cassagno N, Deloire MS, Vekris A, Biran M, Raffard G, Brochet B, Canron MH, Franconi JM, Boiziau C, Petry KG (2011) Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult Scler 17:2–15
  Article CAS PubMed Google Scholar
• Mittrucker HW, Visekruna A, Huber M (2014) Heterogeneity in the differentiation and function of CD8(+) T cells. Arch Immunol Ther Exp (Warsz) 62:449–458
  Article CAS Google Scholar
• Miyazaki Y, Miyake S, Chiba A, Lantz O, Yamamura T (2011) Mucosal-associated invariant T cells regulate Th1 response in multiple sclerosis. Int Immunol 23:529–535
  Article CAS PubMed Google Scholar
• Mohammad MG, Tsai VW, Ruitenberg MJ, Hassanpour M, Li H, Hart PH, Breit SN, Sawchenko PE, Brown DA (2014) Immune cell trafficking from the brain maintains CNS immune tolerance. J Clin Invest 124:1228–1241
  Article PubMed Central CAS PubMed Google Scholar
• Monteyne P, Van Antwerpen MP, Sindic CJ (1999) Expression of costimulatory molecules and cytokines in CSF and peripheral blood mononuclear cells from multiple sclerosis patients. Acta Neurol Belg 99:11–20
  CAS PubMed Google Scholar
• Moreno M, Bannerman P, Ma J, Guo F, Miers L, Soulika AM, Pleasure D (2014) Conditional ablation of astroglial CCL2 suppresses CNS accumulation of M1 macrophages and preserves axons in mice with MOG peptide EAE. J Neurosci 34:8175–8185
  Article PubMed Central PubMed CAS Google Scholar
• Multiple Sclerosis International Federation (2013) Atlas of MS 2013. In, http://www.msif.org/includes/documents/cm_docs/2013/m/msif-atlas-of-ms-2013-report.pdf?f=1 Edition (Federation MSI, ed). http://www.msif.org/includes/documents/cm_docs/2013/m/msif-atlas-of-ms-2013-report.pdf?f=1
• Murphy AC, Lalor SJ, Lynch MA, Mills KH (2010) Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis. Brain Behav Immun 24:641–651
  Article CAS PubMed Google Scholar
• Murray PD, Pavelko KD, Leibowitz J, Lin X, Rodriguez M (1998) CD4(+) and CD8(+) T cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis. J Virol 72:7320–7329
  PubMed Central CAS PubMed Google Scholar
• Najafian N, Chitnis T, Salama AD, Zhu B, Benou C, Yuan X, Clarkson MR, Sayegh MH, Khoury SJ (2003) Regulatory functions of CD8 + CD28- T cells in an autoimmune disease model. J Clin Invest 112:1037–1048
  Article PubMed Central CAS PubMed Google Scholar
• Nakagawa Y, Chiba K (2014) Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases. Pharmaceuticals 7:1028–1048
  Article PubMed Central CAS PubMed Google Scholar
• Neumann H, Medana IM, Bauer J, Lassmann H (2002) Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci 25:313–319
  Article CAS PubMed Google Scholar
• Nicholson LB, Greer JM, Sobel RA, Lees MB, Kuchroo VK (1995) An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 3:397–405
  Article CAS PubMed Google Scholar
• Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, Burroughs AR, Foureau DM, Haque-Begum S, Kasper LH (2009) Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol 183:6041–6050
  Article CAS PubMed Google Scholar
• Ochoa-Reparaz J, Mielcarz DW, Wang Y, Begum-Haque S, Dasgupta S, Kasper DL, Kasper LH (2010) A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol 3:487–495
  Article CAS PubMed Google Scholar
• Olivares-Villagomez D, Wang Y, Lafaille JJ (1998) Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis. J Exp Med 188:1883–1894
  Article PubMed Central CAS PubMed Google Scholar
• Olson JK, Croxford JL, Calenoff MA, Dal Canto MC, Miller SD (2001) A virus-induced molecular mimicry model of multiple sclerosis. J Clin Invest 108:311–318
  Article PubMed Central CAS PubMed Google Scholar
• Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA (1990) T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346:183–187
  Article CAS PubMed Google Scholar
• Panitch HS, Hirsch RL, Haley AS, Johnson KP (1987a) Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1:893–895
  Article CAS PubMed Google Scholar
• Panitch HS, Hirsch RL, Schindler J, Johnson KP (1987b) Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology 37:1097–1102
  Article CAS PubMed Google Scholar
• Pierson E, Simmons SB, Castelli L, Goverman JM (2012) Mechanisms regulating regional localization of inflammation during CNS autoimmunity. Immunol Rev 248:205–215
  Article PubMed Central PubMed Google Scholar
• Pierson ER, Stromnes IM, Goverman JM (2014) B cells promote induction of experimental autoimmune encephalomyelitis by facilitating reactivation of T cells in the central nervous system. J Immunol 192:929–939
  Article PubMed Central CAS PubMed Google Scholar
• Pittet CL, Newcombe J, Antel JP, Arbour N (2011) The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD-L1 levels on CNS cells. Glia 59:841–856
  Article PubMed Google Scholar
• Politis M, Giannetti P, Su P, Turkheimer F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini P (2012) Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology 79:523–530
  Article PubMed Central PubMed Google Scholar
• Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW, Investigators A (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899–910
  Article CAS PubMed Google Scholar
• Ponomarev ED, Shriver LP, Maresz K, Dittel BN (2005) Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J Neurosci Res 81:374–389
  Article CAS PubMed Google Scholar
• Raivich G, Banati R (2004) Brain microglia and blood-derived macrophages: molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease. Brain Res Brain Res Rev 46:261–281
  Article CAS PubMed Google Scholar
• Ransohoff RM, Estes ML (1991) Astrocyte expression of major histocompatibility complex gene products in multiple sclerosis brain tissue obtained by stereotactic biopsy. Arch Neurol 48:1244–1246
  Article CAS PubMed Google Scholar
• Raphael I, Nalawade S, Eagar TN, Forsthuber TG (2014) T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine S1043–4666(14):00539
  Google Scholar
• Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, Uccelli A, Lanzavecchia A, Engelhardt B, Sallusto F (2009) C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10:514–523
  Article CAS PubMed Google Scholar
• Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L, Sobel RA, Wucherpfennig KW, Kuchroo VK (2004) Myelin proteolipid protein-specific CD4 + CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 101:15434–15439
  Article PubMed Central CAS PubMed Google Scholar
• Rep MH, van Oosten BW, Roos MT, Ader HJ, Polman CH, van Lier RA (1997) Treatment with depleting CD4 monoclonal antibody results in a preferential loss of circulating naive T cells but does not affect IFN-gamma secreting TH1 cells in humans. J Clin Invest 99:2225–2231
  Article PubMed Central CAS PubMed Google Scholar
• Rivers TM, Sprunt DH, Berry GP (1933) Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exp Med 58:39–53
  Article PubMed Central CAS PubMed Google Scholar
• Roy A, Liu X, Pahan K (2007) Myelin basic protein-primed T cells induce neurotrophins in glial cells via alphavbeta3 [corrected] integrin. J Biol Chem 282:32222–32232
  Article PubMed Central CAS PubMed Google Scholar
• Rubio JP, Bahlo M, Stankovich J, Burfoot RK, Johnson LJ, Huxtable S, Butzkueven H, Lin L, Taylor BV, Speed TP, Kilpatrick TJ, Mignot E, Foote SJ (2007) Analysis of extended HLA haplotypes in multiple sclerosis and narcolepsy families confirms a predisposing effect for the class I region in Tasmanian MS patients. Immunogenetics 59:177–186
  Article CAS PubMed Google Scholar
• Rumah KR, Linden J, Fischetti VA, Vartanian T (2013) Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PLoS One 8:e76359
  Article PubMed Central CAS PubMed Google Scholar
• Saikali P, Antel JP, Newcombe J, Chen Z, Freedman M, Blain M, Cayrol R, Prat A, Hall JA, Arbour N (2007) NKG2D-mediated cytotoxicity toward oligodendrocytes suggests a mechanism for tissue injury in multiple sclerosis. J Neurosci 27:1220–1228
  Article CAS PubMed Google Scholar
• Saikali P, Antel JP, Pittet CL, Newcombe J, Arbour N (2010) Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis. J Immunol 185:5693–5703
  Article CAS PubMed Google Scholar
• Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763
  Article CAS PubMed Google Scholar
• Sauer BM, Schmalstieg WF, Howe CL (2013) Axons are injured by antigen-specific CD8(+) T cells through a MHC class I- and granzyme B-dependent mechanism. Neurobiol Dis 59:194–205
  Article PubMed Central CAS PubMed Google Scholar
• Sawcer S, Franklin RJ, Ban M (2014) Multiple sclerosis genetics. Lancet Neurol 13:700–709
  Article CAS PubMed Google Scholar
• Schneider-Hohendorf T, Stenner MP, Weidenfeller C, Zozulya AL, Simon OJ, Schwab N, Wiendl H (2010) Regulatory T cells exhibit enhanced migratory characteristics, a feature impaired in patients with multiple sclerosis. Eur J Immunol 40:3581–3590
  Article CAS PubMed Google Scholar
• Schneider-Hohendorf T, Rossaint J, Mohan H, Boning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, Zarbock A, Schwab N, Wiendl H (2014) VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells. J Exp Med 211:1833–1846
  Article PubMed Central CAS PubMed Google Scholar
• Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A, de St F, Groth B (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203:1693–1700
  Article PubMed Central CAS PubMed Google Scholar
• Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH, Ustekinumab MSI (2008) Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 7:796–804
  Article CAS PubMed Google Scholar
• Sharief MK, Thompson EJ (1993) Correlation of interleukin-2 and soluble interleukin-2 receptor with clinical activity of multiple sclerosis. J Neurol Neurosurg Psychiatry 56:169–174
  Article PubMed Central CAS PubMed Google Scholar
• Shevach EM, Thornton AM (2014) tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev 259:88–102
  Article PubMed Central CAS PubMed Google Scholar
• Shinohara ML, Kim JH, Garcia VA, Cantor H (2008) Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 29:68–78
  Article PubMed Central CAS PubMed Google Scholar
• Sinha S, Itani FR, Karandikar NJ (2014) Immune regulation of multiple sclerosis by CD8+ T cells. Immunol Res 59:254–265
  Article PubMed Central CAS PubMed Google Scholar
• Skulina C, Schmidt S, Dornmair K, Babbe H, Roers A, Rajewsky K, Wekerle H, Hohlfeld R, Goebels N (2004) Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. Proc Natl Acad Sci U S A 101:2428–2433
  Article PubMed Central CAS PubMed Google Scholar
• Sonderegger I, Kisielow J, Meier R, King C, Kopf M (2008) IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol 38:1833–1838
  Article CAS PubMed Google Scholar
• Stoolman JS, Duncker PC, Huber AK, Segal BM (2014) Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis. J Immunol 193:564–570
  Article PubMed Central CAS PubMed Google Scholar
• Strachan-Whaley M, Rivest S, Yong VW (2014) Interactions between microglia and T cells in multiple sclerosis pathobiology. J Interferon Cytokine Res 34:615–622
  Article CAS PubMed Google Scholar
• Stromnes IM, Goverman JM (2006a) Passive induction of experimental allergic encephalomyelitis. Nat Protoc 1:1952–1960
  Article CAS PubMed Google Scholar
• Stromnes IM, Goverman JM (2006b) Active induction of experimental allergic encephalomyelitis. Nat Protoc 1:1810–1819
  Article CAS PubMed Google Scholar
• Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM (2008) Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med 14:337–342
  Article PubMed Central CAS PubMed Google Scholar
• Strunk T, Bubel S, Mascher B, Schlenke P, Kirchner H, Wandinger KP (2000) Increased numbers of CCR5+ interferon-gamma- and tumor necrosis factor-alpha-secreting T lymphocytes in multiple sclerosis patients. Ann Neurol 47:269–273
  Article CAS PubMed Google Scholar
• Stumhofer JS, Silver JS, Laurence A, Porrett PM, Harris TH, Turka LA, Ernst M, Saris CJ, O’Shea JJ, Hunter CA (2007) Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 8:1363–1371
  Article CAS PubMed Google Scholar
• Sun JB, Olsson T, Wang WZ, Xiao BG, Kostulas V, Fredrikson S, Ekre HP, Link H (1991) Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls. Eur J Immunol 21:1461–1468
  Article CAS PubMed Google Scholar
• Sun D, Whitaker JN, Huang Z, Liu D, Coleclough C, Wekerle H, Raine CS (2001) Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. J Immunol 166:7579–7587
  Article CAS PubMed Google Scholar
• Sweeney CM, Lonergan R, Basdeo SA, Kinsella K, Dungan LS, Higgins SC, Kelly PJ, Costelloe L, Tubridy N, Mills KH, Fletcher JM (2011) IL-27 mediates the response to IFN-beta therapy in multiple sclerosis patients by inhibiting Th17 cells. Brain Behav Immun 25:1170–1181
  Article CAS PubMed Google Scholar
• Takata K, Kinoshita M, Okuno T, Moriya M, Kohda T, Honorat JA, Sugimoto T, Kumanogoh A, Kayama H, Takeda K, Sakoda S, Nakatsuji Y (2011) The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells. PLoS One 6:e27644
  Article PubMed Central CAS PubMed Google Scholar
• Talbot PJ, Paquette JS, Ciurli C, Antel JP, Ouellet F (1996) Myelin basic protein and human coronavirus 229E cross-reactive T cells in multiple sclerosis. Ann Neurol 39:233–240
  Article CAS PubMed Google Scholar
• Tennakoon DK, Mehta RS, Ortega SB, Bhoj V, Racke MK, Karandikar NJ (2006) Therapeutic induction of regulatory, cytotoxic CD8+ T cells in multiple sclerosis. J Immunol 176:7119–7129
  Article CAS PubMed Google Scholar
• Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, Affaticati P, Gilfillan S, Lantz O (2003) Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164–169
  Article CAS PubMed Google Scholar
• Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172:146–155
  Article PubMed Central CAS PubMed Google Scholar
• van Noort JM, van den Elsen PJ, van Horssen J, Geurts JJ, van der Valk P, Amor S (2011) Preactive multiple sclerosis lesions offer novel clues for neuroprotective therapeutic strategies. CNS Neurol Disord Drug Targets 10:68–81
  Article PubMed Google Scholar
• van Oosten BW, Lai M, Hodgkinson S, Barkhof F, Miller DH, Moseley IF, Thompson AJ, Rudge P, McDougall A, McLeod JG, Ader HJ, Polman CH (1997) Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cM-T412: results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial. Neurology 49:351–357
  Article PubMed Google Scholar
• van Zwam M, Huizinga R, Heijmans N, van Meurs M, Wierenga-Wolf AF, Melief MJ, Hintzen RQ, t Hart BA, Amor S, Boven LA, Laman JD (2009a) Surgical excision of CNS-draining lymph nodes reduces relapse severity in chronic-relapsing experimental autoimmune encephalomyelitis. J Pathol 217:543–551
  Article PubMed Google Scholar
• van Zwam M, Huizinga R, Melief MJ, Wierenga-Wolf AF, van Meurs M, Voerman JS, Biber KP, Boddeke HW, Hopken UE, Meisel C, Meisel A, Bechmann I, Hintzen RQ, t Hart BA, Amor S, Laman JD, Boven LA (2009b) Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE. J Mol Med (Berl) 87:273–286
  Article CAS Google Scholar
• Vanderlugt CL, Neville KL, Nikcevich KM, Eagar TN, Bluestone JA, Miller SD (2000) Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J Immunol 164:670–678
  Article CAS PubMed Google Scholar
• Vandevyver C, Mertens N, van den Elsen P, Medaer R, Raus J, Zhang J (1995) Clonal expansion of myelin basic protein-reactive T cells in patients with multiple sclerosis: restricted T cell receptor V gene rearrangements and CDR3 sequence. Eur J Immunol 25:958–968
  Article CAS PubMed Google Scholar
• Vasanthakumar A, Kallies A (2013) IL-27 paves different roads to Tr1. Eur J Immunol 43:882–885
  Article CAS PubMed Google Scholar
• Venken K, Hellings N, Broekmans T, Hensen K, Rummens JL, Stinissen P (2008) Natural naive CD4 + CD25 + CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J Immunol 180:6411–6420
  Article CAS PubMed Google Scholar
• Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4 + CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979
  Article PubMed Central CAS PubMed Google Scholar
• Villares R, Cadenas V, Lozano M, Almonacid L, Zaballos A, Martinez AC, Varona R (2009) CCR6 regulates EAE pathogenesis by controlling regulatory CD4+ T-cell recruitment to target tissues. Eur J Immunol 39:1671–1681
  Article CAS PubMed Google Scholar
• Vollmer TL, Wynn DR, Alam MS, Valdes J (2011) A phase 2, 24-week, randomized, placebo-controlled, double-blind study examining the efficacy and safety of an anti-interleukin-12 and −23 monoclonal antibody in patients with relapsing-remitting or secondary progressive multiple sclerosis. Mult Scler 17:181–191
  Article CAS PubMed Google Scholar
• Walker LS, Abbas AK (2002) The enemy within: keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol 2:11–19
  Article CAS PubMed Google Scholar
• Willenborg DO, Fordham S, Bernard CC, Cowden WB, Ramshaw IA (1996) IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J Immunol 157:3223–3227
  CAS PubMed Google Scholar
• Williams K, Ulvestad E, Antel JP (1994) B7/BB-1 antigen expression on adult human microglia studied in vitro and in situ. Eur J Immunol 24:3031–3037
  Article CAS PubMed Google Scholar
• Willing A, Friese MA (2012) CD8-mediated inflammatory central nervous system disorders. Curr Opin Neurol 25:316–321
  Article CAS PubMed Google Scholar
• Willing A, Leach OA, Ufer F, Attfield KE, Steinbach K, Kursawe N, Piedavent M, Friese MA (2014) CD8(+) MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis. Eur J Immunol 44:3119–3128
  Article CAS PubMed Google Scholar
• Wlodarczyk A, Lobner M, Cedile O, Owens T (2014) Comparison of microglia and infiltrating CD11c(+) cells as antigen presenting cells for T cell proliferation and cytokine response. J Neuroinflammation 11:57
  Article PubMed Central PubMed CAS Google Scholar
• Wong D, Dorovini-Zis K (1992) Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide. J Neuroimmunol 39:11–21
  Article CAS PubMed Google Scholar
• Wong D, Dorovini-Zis K (1995) Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture. Microvasc Res 49:325–339
  Article CAS PubMed Google Scholar
• Wu GF, Alvarez E (2011) The immunopathophysiology of multiple sclerosis. Neurol Clin 29:257–278
  Article PubMed Central PubMed Google Scholar
• Wu GF, Dandekar AA, Pewe L, Perlman S (2000) CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination. J Immunol 165:2278–2286
  Article CAS PubMed Google Scholar
• Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695–705
  Article CAS PubMed Google Scholar
• Wulff H, Calabresi PA, Allie R, Yun S, Pennington M, Beeton C, Chandy KG (2003) The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS. J Clin Invest 111:1703–1713
  Article PubMed Central CAS PubMed Google Scholar
• Yu M, Johnson JM, Tuohy VK (1996) A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. J Exp Med 183:1777–1788
  Article CAS PubMed Google Scholar
• Yu P, Bamford RN, Waldmann TA (2014) IL-15-dependent CD8+ CD122+ T cells ameliorate experimental autoimmune encephalomyelitis by modulating IL-17 production by CD4+ T cells. Eur J Immunol 44:3330–3341
  Article CAS PubMed Google Scholar
• Zaguia F, Saikali P, Ludwin S, Newcombe J, Beauseigle D, McCrea E, Duquette P, Prat A, Antel JP, Arbour N (2013) Cytotoxic NKG2C+ CD4 T cells target oligodendrocytes in multiple sclerosis. J Immunol 190:2510–2518
  Article CAS PubMed Google Scholar
• Zang YC, Li S, Rivera VM, Hong J, Robinson RR, Breitbach WT, Killian J, Zhang JZ (2004) Increased CD8+ cytotoxic T cell responses to myelin basic protein in multiple sclerosis. J Immunol 172:5120–5127
  Article CAS PubMed Google Scholar
• Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA (1994) Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 179:973–984
  Article CAS PubMed Google Scholar

Download references