The enemy within: keeping self-reactive T cells at bay in the periphery (original) (raw)
Arstila, T. P. et al. A direct estimate of the human αβT cell receptor diversity. Science286, 958–961 (1999). CASPubMed Google Scholar
Mason, D. A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today19, 395–404 (1998). CASPubMed Google Scholar
Derbinski, J., Schulte, A., Kyewski, B. & Klein, L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nature Immunol.2, 1032–1039 (2001). CAS Google Scholar
Lohmann, T., Leslie, R. D. & Londei, M. T cell clones to epitopes of glutamic acid decarboxylase 65 raised from normal subjects and patients with insulin-dependent diabetes. J. Autoimmun.9, 385–389 (1996). CASPubMed Google Scholar
Semana, G., Gausling, R., Jackson, R. A. & Hafler, D. A. T cell autoreactivity to proinsulin epitopes in diabetic patients and healthy subjects. J. Autoimmun.12, 259–267 (1999). CASPubMed Google Scholar
Bouneaud, C., Kourilsky, P. & Bousso, P. Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion. Immunity13, 829–840 (2000). CASPubMed Google Scholar
Alferink, J. et al. Control of neonatal tolerance to tissue antigens by peripheral T cell trafficking. Science282, 1338–1341 (1998). CASPubMed Google Scholar
Kurts, C., Miller, J. F., Subramaniam, R. M., Carbone, F. R. & Heath, W. R. Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction. J. Exp. Med.188, 409–414 (1998). CASPubMedPubMed Central Google Scholar
Hoglund, P. et al. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J. Exp. Med.. 189, 331–339 (1999).Pancreatic, but not renal, antigen presentation is compromised in juvenile mice, probably explaining the delay in onset of disease in diabetes-prone mouse strains. CASPubMedPubMed Central Google Scholar
Andre, I. et al. Checkpoints in the progression of autoimmune disease: lessons from diabetes models. Proc. Natl Acad. Sci. USA93, 2260–2263 (1996). CASPubMedPubMed Central Google Scholar
Jenkins, M. K. & Schwartz, R. H. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med.165, 302–319 (1987). CASPubMed Google Scholar
Lane, P., Haller, C. & McConnell, F. Evidence that induction of tolerance in vivo involves active signaling via a B7 ligand-dependent mechanism: CTLA4–Ig protects Vβ8+ T cells from tolerance induction by the superantigen staphylococcal enterotoxin B. Eur. J. Immunol.26, 858–862 (1996). CASPubMed Google Scholar
Krummel, M. F. & Allison, J. P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med.182, 459–465 (1995). CASPubMed Google Scholar
Walunas, T. L., Bakker, C. Y. & Bluestone, J. A. CTLA-4 ligation blocks CD28-dependent T cell activation. J. Exp. Med.183, 2541–2550 (1996). CASPubMed Google Scholar
Perez, V. L. et al. Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity6, 411–417 (1997). CASPubMed Google Scholar
Walunas, T. L. & Bluestone, J. A. CTLA-4 regulates tolerance induction and T cell differentiation in vivo. J. Immunol.160, 3855–3860 (1998). CASPubMed Google Scholar
Tivol, E. A. et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity3, 541–547 (1995). CASPubMed Google Scholar
Waterhouse, P. et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science270, 985–988 (1995). CASPubMed Google Scholar
Lechner, O. et al. Fingerprints of anergic T cells. Curr. Biol.11, 587–595 (2001). CASPubMed Google Scholar
Nishimura, H., Nose, M., Hiai, H., Minato, N. & Honjo, T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity11, 141–151 (1999).Mice on a C57/BL6 background that lack PD-1 exhibit glomerulonephritis and arthritis that is exacerbated if the Fas pathway is also defective. Lymphocytic infiltration of multiple organs is observed in 2C TCR transgenic mice that lack PD–1. CASPubMed Google Scholar
Nishimura, H. et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science291, 319–322 (2001). CASPubMed Google Scholar
Freeman, G. J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med.192, 1027–1034 (2000). CASPubMedPubMed Central Google Scholar
Latchman, Y. et al. PD-L2 is a second ligand for PD-I and inhibits T cell activation. Nature Immunol.2, 261–268 (2001). CAS Google Scholar
Chambers, C. A. The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol.22, 217–223 (2001). CASPubMed Google Scholar
Pape, K. A., Merica, R., Mondino, A., Khoruts, A. & Jenkins, M. K. Direct evidence that functionally impaired CD4+ T cells persist in vivo following induction of peripheral tolerance. J. Immunol.160, 4719–4729 (1998).CD4+ OVA-specific TCR transgenic T cells persistin vivofor several months following tolerogenic administration of soluble OVA peptide. CASPubMed Google Scholar
Young, D. A. et al. IL-4, IL-10, IL-13, and TGF-β from an altered peptide ligand- specific TH2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis. J. Immunol.164, 3563–3572 (2000). CASPubMed Google Scholar
Bradley, L. M. et al. Islet-specific TH1, but not TH2, cells secrete multiple chemokines and promote rapid induction of autoimmune diabetes. J. Immunol.162, 2511–2520 (1999). CASPubMed Google Scholar
Pakala, S. V., Kurrer, M. O. & Katz, J. D. T helper 2 (TH2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) mice. J. Exp. Med.186, 299–306 (1997). CASPubMedPubMed Central Google Scholar
Charles, P. C., Weber, K. S., Cipriani, B. & Brosnan, C. F. Cytokine, chemokine and chemokine receptor mRNA expression in different strains of normal mice: implications for establishment of a TH1/TH2 bias. J. Neuroimmunol.100, 64–73 (1999). CASPubMed Google Scholar
Chensue, S. W. et al. Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice. J. Exp. Med.193, 573–584 (2001). CASPubMedPubMed Central Google Scholar
Kearney, E. R., Pape, K. A., Loh, D. Y. & Jenkins, M. K. Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity1, 327–339 (1994). CASPubMed Google Scholar
Walker, L. S. et al. Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. J. Exp. Med.190, 1115–1122 (1999). CASPubMedPubMed Central Google Scholar
Ansel, K. M., McHeyzer-Williams, L. J., Ngo, V. N., McHeyzer-Williams, M. G. & Cyster, J. G. _in vivo_-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. J. Exp. Med.190, 1123–1134 (1999). CASPubMedPubMed Central Google Scholar
Luther, S. A., Lopez, T., Bai, W., Hanahan, D. & Cyster, J. G. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity12, 471–481 (2000). CASPubMed Google Scholar
Ishikawa, S. et al. Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) by C11b+CD11c+ dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC. J. Exp. Med.193, 1393–1402 (2001). CASPubMedPubMed Central Google Scholar
Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A. & Nagata, S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature356, 314–317 (1992).First direct evidence for a non-redundant role of the Fas pathway in maintaining self-tolerance. CASPubMed Google Scholar
Sobel, E. S., Kakkanaiah, V. N., Cohen, P. L. & Eisenberg, R. A. Correction of gld autoimmunity by co-infusion of normal bone marrow suggests that gld is a mutation of the Fas ligand gene. Int. Immunol.5, 1275–1278 (1993). CASPubMed Google Scholar
Suda, T., Takahashi, T., Golstein, P. & Nagata, S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell75, 1169–1178 (1993). CASPubMed Google Scholar
Fisher, G. H. et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell81, 935–946 (1995). CASPubMed Google Scholar
Suzuki, A. et al. T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity14, 523–534 (2001). CASPubMed Google Scholar
Chen, W. et al. Requirement for transforming growth factor β1 in controlling T cell apoptosis. J. Exp. Med.194, 439–454 (2001). CASPubMedPubMed Central Google Scholar
Lenardo, M. J. Interleukin-2 programs mouse αβ T lymphocytes for apoptosis. Nature353, 858–861 (1991). CASPubMed Google Scholar
Van Parijs, L. et al. Functional responses and apoptosis of CD25 (IL-2Rα)-deficient T cells expressing a transgenic antigen receptor. J. Immunol.158, 3738–3745 (1997). CASPubMed Google Scholar
Van Parijs, L. et al. Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death. Immunity11, 281–288 (1999). CASPubMed Google Scholar
Refaeli, Y., Van Parijs, L., London, C. A., Tschopp, J. & Abbas, A. K. Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis. Immunity8, 615–623 (1998). CASPubMed Google Scholar
Sadlack, B. et al. Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells. Eur. J. Immunol.25, 3053–3059 (1995). CASPubMed Google Scholar
Willerford, D. M. et al. Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartment. Immunity3, 521–530 (1995). CASPubMed Google Scholar
Malek, T. R., Porter, B. O., Codias, E. K., Scibelli, P. & Yu, A. Normal lymphoid homeostasis and lack of lethal autoimmunity in mice containing mature T cells with severely impaired IL-2 receptors. J. Immunol.164, 2905–2914 (2000). CASPubMed Google Scholar
Singer, G. G. & Abbas, A. K. The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity1, 365–371 (1994).In vivopeptide administration induces thymic deletion even in the absence of Fas signalling, but peripheral T-cell deletion is impaired. CASPubMed Google Scholar
Mogil, R. J. et al. Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo. Int. Immunol.7, 1451–1458 (1995). CASPubMed Google Scholar
Ettinger, R. et al. Fas ligand-mediated cytotoxicity is directly responsible for apoptosis of normal CD4+ T cells responding to a bacterial superantigen. J. Immunol.154, 4302–4308 (1995). CASPubMed Google Scholar
Hildeman, D. A. et al. Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity10, 735–744 (1999). CASPubMed Google Scholar
Van Parijs, L., Peterson, D. A. & Abbas, A. K. The Fas/Fas ligand pathway and Bcl-2 regulate T cell responses to model self and foreign antigens. Immunity8, 265–274 (1998). CASPubMed Google Scholar
Janeway, C. A. Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol. Today13, 11–16 (1992). CASPubMed Google Scholar
Medzhitov, R., Preston-Hurlburt, P. & Janeway, C. A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature388, 394–397 (1997).Cloning and characterization of a human homologue of theDrosophilaToll protein that can activate the NF-κB pathway. CASPubMed Google Scholar
Aderem, A. & Ulevitch, R. J. Toll-like receptors in the induction of the innate immune response. Nature406, 782–787 (2000). CASPubMed Google Scholar
Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science282, 2085–2088 (1998). CASPubMed Google Scholar
Matzinger, P. Tolerance, danger, and the extended family. Annu. Rev. Immunol.12, 991–1045 (1994). CASPubMed Google Scholar
Basu, S., Binder, R. J., Suto, R., Anderson, K. M. & Srivastava, P. K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int. Immunol.12, 1539–1546 (2000). CASPubMed Google Scholar
Kurts, C. et al. Constitutive class I-restricted exogenous presentation of self antigens in vivo. J. Exp. Med.184, 923–930 (1996).First demonstration of how tissue-associated antigens, which are not accessible to recirculating T cells, can be presented by bone-marrow-derived APCs to CD8 T cells in the context of MHC class I. CASPubMed Google Scholar
Adler, A. J. et al. CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells. J. Exp. Med.187, 1555–1564 (1998). CASPubMedPubMed Central Google Scholar
Kurts, C., Cannarile, M., Klebba, I. & Brocker, T. Dendritic cells are sufficient to cross-present self-antigens to CD8 T cells in vivo. J. Immunol.166, 1439–1442 (2001). CASPubMed Google Scholar
Hirao, M. et al. CC chemokine receptor-7 on dendritic cells is induced after interaction with apoptotic tumor cells: critical role in migration from the tumor site to draining lymph nodes. Cancer Res.60, 2209–2217 (2000). CASPubMed Google Scholar
Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nature Med.5, 1249–1255 (1999). CASPubMed Google Scholar
Sauter, B. et al. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med.191, 423–434 (2000). CASPubMedPubMed Central Google Scholar
Huang, F. P. et al. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J. Exp. Med.191, 435–444 (2000). CASPubMedPubMed Central Google Scholar
Inaba, K. et al. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J. Exp. Med.188, 2163–2173 (1998). CASPubMedPubMed Central Google Scholar
Thery, C. et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein HSC 73. J. Cell Biol.147, 599–610 (1999). CASPubMedPubMed Central Google Scholar
Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, C. & Bhardwaj, N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med.193, 233–238 (2001). CASPubMedPubMed Central Google Scholar
Asano, M., Toda, M., Sakaguchi, N. & Sakaguchi, S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med.184, 387–396 (1996).Removal of the thymus at day 3 after birth eliminates the regulatory CD4+CD25+ cell subset from the periphery and is associated with onset of autoimmunity that can be prevented by inoculation with CD25+ cells from normal mice. CASPubMed Google Scholar
Thornton, A. M. & Shevach, E. M. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol.164, 183–190 (2000). CASPubMed Google Scholar
Thornton, A. M. & Shevach, E. M. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med.188, 287–296 (1998). CASPubMedPubMed Central Google Scholar
Kuniyasu, Y. et al. Naturally anergic and suppressive CD25+CD4+ T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. Int. Immunol.12, 1145–1155 (2000). CASPubMed Google Scholar
Salomon, B. et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity12, 431–440 (2000). CASPubMed Google Scholar
Read, S., Malmstrom, V. & Powrie, F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J. Exp. Med.192, 295–302 (2000). CASPubMedPubMed Central Google Scholar
Takahashi, T. et al. Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med.192, 303–310 (2000). CASPubMedPubMed Central Google Scholar
Greenwald, R. J., Boussiotis, V. A., Lorsbach, R. B., Abbas, A. K. & Sharpe, A. H. CTLA-4 regulates induction of anergy in vivo. Immunity14, 145–155 (2001). CASPubMed Google Scholar
Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature389, 737–742 (1997). CASPubMed Google Scholar
Wakkach, A., Cottrez, F. & Groux, H. Differentiation of regulatory T cells 1 is induced by CD2 costimulation. J. Immunol.167, 3107–3113 (2001). CASPubMed Google Scholar
Groux, H., Bigler, M., de Vries, J. E. & Roncarolo, M. G. Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J. Immunol.160, 3188–3193 (1998). CASPubMed Google Scholar
Jonuleit, H., Schmitt, E., Schuler, G., Knop, J. & Enk, A. H. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med.192, 1213–1222 (2000). CASPubMedPubMed Central Google Scholar
Powrie, F., Carlino, J., Leach, M. W., Mauze, S. & Coffman, R. L. A critical role for transforming growth factor-β but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RBlow CD4+ T cells. J. Exp. Med.183, 2669–2674 (1996).Colitis induced by CD45RBhicells in SCID mice is prevented by co-transfer of CD45RBlowcells: IL-10 and TGF-β are required for this effect. CASPubMed Google Scholar
Asseman, C., Mauze, S., Leach, M. W., Coffman, R. L. & Powrie, F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med.190, 995–1004 (1999). CASPubMedPubMed Central Google Scholar
Quinn, A. et al. Regulatory and effector CD4 T cells in nonobese diabetic mice recognize overlapping determinants on glutamic acid decarboxylase and use distinct Vβ genes. J. Immunol.166, 2982–2991 (2001). CASPubMed Google Scholar
Miller, S. D. et al. Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading. Nature Med.3, 1133–1136 (1997). CASPubMed Google Scholar
Zhao, Z. S., Granucci, F., Yeh, L., Schaffer, P. A. & Cantor, H. Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science279, 1344–1347 (1998). CASPubMed Google Scholar
Bachmaier, K. et al. Chlamydia infections and heart disease linked through antigenic mimicry. Science283, 1335–1339 (1999). CASPubMed Google Scholar
Hemmer, B. et al. Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology. J. Immunol.160, 3631–3636 (1998). CASPubMed Google Scholar
Hiemstra, H. S. et al. Quantitative determination of TCR cross-reactivity using peptide libraries and protein databases. Eur. J. Immunol.29, 2385–2391 (1999). CASPubMed Google Scholar
Steere, A. C., Gross, D., Meyer, A. L. & Huber, B. T. Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis. J. Autoimmun.16, 263–268 (2001). CASPubMed Google Scholar
Gautam, A. M., Liblau, R., Chelvanayagam, G., Steinman, L. & Boston, T. A viral peptide with limited homology to a self peptide can induce clinical signs of experimental autoimmune encephalomyelitis. J. Immunol.161, 60–64 (1998). CASPubMed Google Scholar
Panoutsakopoulou, V. et al. Analysis of the relationship between viral infection and autoimmune disease. Immunity15, 137–147 (2001). CASPubMed Google Scholar
Keffer, J. et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J.10, 4025–4031 (1991). CASPubMedPubMed Central Google Scholar
Horwitz, M. S. et al. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nature Med.4, 781–785 (1998). CASPubMed Google Scholar
Ehl, S. et al. Viral and bacterial infections interfere with peripheral tolerance induction and activate CD8+ T cells to cause immunopathology. J. Exp. Med.187, 763–774 (1998). CASPubMedPubMed Central Google Scholar
Shi, F. D. et al. Natural killer cells determine the outcome of B cell-mediated autoimmunity. Nature Immunol.1, 245–251 (2000). CAS Google Scholar
Gombert, J. M. et al. Early quantitative and functional deficiency of NK1+-like thymocytes in the NOD mouse. Eur. J. Immunol.26, 2989–2998 (1996). CASPubMed Google Scholar
Lehuen, A. et al. Overexpression of natural killer T cells protects Vα14-Jα281 transgenic nonobese diabetic mice against diabetes. J. Exp. Med.188, 1831–1839 (1998). CASPubMedPubMed Central Google Scholar
Wang, B., Geng, Y. B. & Wang, C. R. CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes. J. Exp. Med.194, 313–320 (2001). PubMedPubMed Central Google Scholar
Jordan, M. S. et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nature Immunol.2, 301–306 (2001). CAS Google Scholar
Bensinger, S. J., Bandeira, A., Jordan, M. S., Caton, A. J. & Laufer, T. M. Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4+25+ immunoregulatory T cells. J. Exp. Med.194, 427–438 (2001). CASPubMedPubMed Central Google Scholar
Kumanogoh, A. et al. Increased T cell autoreactivity in the absence of CD40–CD40 ligand interactions: a role of CD40 in regulatory T cell development. J. Immunol.166, 353–360 (2001). CASPubMed Google Scholar