Organization of immunological memory by bone marrow stroma (original) (raw)
Friedenstein, A. J., Chailakhyan, R. K., Latsinik, N. V., Panasyuk, A. F. & Keiliss-Borok, I. V. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation17, 331–340 (1974). CASPubMed Google Scholar
Mueller, S. N. & Germain, R. N. Stromal cell contributions to the homeostasis and functionality of the immune system. Nature Rev. Immunol.9, 618–629 (2009). ArticleCAS Google Scholar
Ahmed, R. & Gray, D. Immunological memory and protective immunity: understanding their relation. Science272, 54–60 (1996). ArticleCASPubMed Google Scholar
Radbruch, A. et al. Competence and competition: the challenge of becoming a long-lived plasma cell. Nature Rev. Immunol.6, 741–750 (2006). ArticleCAS Google Scholar
Kalia, V., Sarkar, S., Gourley, T. S., Rouse, B. T. & Ahmed, R. Differentiation of memory B and T cells. Curr. Opin. Immunol.18, 255–264 (2006). ArticleCASPubMed Google Scholar
Nakayama, T. & Yamashita, M. Initiation and maintenance of Th2 cell identity. Curr. Opin. Immunol.20, 265–271 (2008). ArticleCASPubMed Google Scholar
Zhou, L., Chong, M. M. & Littman, D. R. Plasticity of CD4+ T cell lineage differentiation. Immunity30, 646–655 (2009). ArticleCASPubMed Google Scholar
Lohning, M. et al. Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J. Exp. Med.205, 53–61 (2008). ArticleCASPubMedPubMed Central Google Scholar
Radbruch, A. & Rajewsky, K. in The Molecular Biology of B cells (eds Alt, F. W., Honjo, T. & Neuberger M.) 247–259 (Elsevier Academic, London, 2004). Google Scholar
Nossal, G. J. Genetic control of lymphopoiesis, plasma cell formation, and antibody production. Int. Rev. Exp. Pathol.1, 1–72 (1962). CASPubMed Google Scholar
Miller, J. J. An autoradiographic study of plasma cell and lymphocyte survival in rat popliteal lymph nodes. J. Immunol.92, 673–681 (1964). PubMed Google Scholar
Holt, P. G., Sedgwick, J. D., O'Leary, C., Krska, K. & Leivers, S. Long-lived IgE- and IgG-secreting cells in rodents manifesting persistent antibody responses. Cell. Immunol.89, 281–289 (1984). ArticleCASPubMed Google Scholar
Ho, F., Lortan, J. E., MacLennan, I. C. & Khan, M. Distinct short-lived and long-lived antibody-producing cell populations. Eur. J. Immunol.16, 1297–1301 (1986). ArticleCASPubMed Google Scholar
Manz, R. A., Thiel, A. & Radbruch, A. Lifetime of plasma cells in the bone marrow. Nature388, 133–134 (1997). This paper shows that plasma cells are long lived and reside in the bone marrow. ArticleCASPubMed Google Scholar
Slifka, M. K., Antia, R., Whitmire, J. K. & Ahmed, R. Humoral immunity due to long-lived plasma cells. Immunity8, 363–372 (1998). ArticleCASPubMed Google Scholar
Manz, R. A., Lohning, M., Cassese, G., Thiel, A. & Radbruch, A. Survival of long-lived plasma cells is independent of antigen. Int. Immunol.10, 1703–1711 (1998). ArticleCASPubMed Google Scholar
Hoyer, B. F. et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J. Exp. Med.199, 1577–1584 (2004). ArticleCASPubMedPubMed Central Google Scholar
Benner, R., Meima, F., van der Meulen, G. M. & van Muiswinkel, W. B. Antibody formation in mouse bone marrow. I. Evidence for the development of plaque-forming cells in situ. Immunology26, 247–255 (1974). CASPubMedPubMed Central Google Scholar
Tokoyoda, K., Egawa, T., Sugiyama, T., Choi, B. I. & Nagasawa, T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity20, 707–718 (2004). This study shows that in the bone marrow CXCL12-expressing mesenchymal stromal cells interact with pre-pro-B cells and plasma cells, and IL-7-expressing mesenchymal stromal cells interact with pro-B cells. ArticleCASPubMed Google Scholar
Tokoyoda, K. et al. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow. Immunity30, 721–730 (2009). This study shows that memory CD4+ T cells are maintained on IL-7-expressing mesenchymal stromal cells. ArticleCASPubMed Google Scholar
Tokoyoda, K., Zehentmeier, S., Chang, H. D. & Radbruch, A. Organization and maintenance of immunological memory by stroma niches. Eur. J. Immunol.39, 2095–2099 (2009). ArticleCASPubMed Google Scholar
Greenberger, J. S. The hematopoietic microenvironment. Crit. Rev. Oncol. Hematol.11, 65–84 (1991). ArticleCASPubMed Google Scholar
Cattoretti, G., Schiro, R., Orazi, A., Soligo, D. & Colombo, M. P. Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro. Blood81, 1726–1738 (1993). CASPubMed Google Scholar
Clark, B. R. & Keating, A. Biology of bone marrow stroma. Ann. NY Acad. Sci.770, 70–78 (1995). ArticleCASPubMed Google Scholar
Krebsbach, P. H., Kuznetsov, S. A., Bianco, P. & Robey, P. G. Bone marrow stromal cells: characterization and clinical application. Crit. Rev. Oral Biol. Med.10, 165–181 (1999). ArticleCASPubMed Google Scholar
Bianco, P., Riminucci, M., Gronthos, S. & Robey, P. G. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells19, 180–192 (2001). ArticleCASPubMed Google Scholar
Morikawa, S. et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J. Exp. Med.206, 2483–2496 (2009). ArticleCASPubMedPubMed Central Google Scholar
Funk, P. E., Stephan, R. P. & Witte, P. L. Vascular cell adhesion molecule 1-positive reticular cells express interleukin-7 and stem cell factor in the bone marrow. Blood86, 2661–2671 (1995). CASPubMed Google Scholar
Honczarenko, M. et al. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells24, 1030–1041 (2006). ArticleCASPubMed Google Scholar
Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science284, 143–147 (1999). ArticleCASPubMed Google Scholar
Bentley, S. A., Alabaster, O. & Foidart, J. M. Collagen heterogeneity in normal human bone marrow. Br. J. Haematol.48, 287–291 (1981). ArticleCASPubMed Google Scholar
Weiss, L. & Chen, L. T. The organization of hematopoietic cords and vascular sinuses in bone marrow. Blood Cells1, 617–638 (1975). Google Scholar
Patt, H. M. & Maloney, M. A. Bone marrow regeneration after local injury: a review. Exp. Hematol.3, 135–148 (1975). CASPubMed Google Scholar
Chan, P. Y. & Aruffo, A. VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin. J. Biol. Chem.268, 24655–24664 (1993). CASPubMed Google Scholar
Springer, T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu. Rev. Physiol.57, 827–872 (1995). ArticleCASPubMed Google Scholar
Jacobsen, K., Kravitz, J., Kincade, P. W. & Osmond, D. G. Adhesion receptors on bone marrow stromal cells: in vivo expression of vascular cell adhesion molecule-1 by reticular cells and sinusoidal endothelium in normal and γ-irradiated mice. Blood87, 73–82 (1996). CASPubMed Google Scholar
Newman, P. J. et al. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science247, 1219–1222 (1990). ArticleCASPubMed Google Scholar
Clark, B. R., Gallagher, J. T. & Dexter, T. M. Cell adhesion in the stromal regulation of haemopoiesis. Baillieres Clin. Haematol.5, 619–652 (1992). ArticleCASPubMed Google Scholar
Zuckerman, K. S. & Wicha, M. S. Extracellular matrix production by the adherent cells of long-term murine bone marrow cultures. Blood61, 540–547 (1983). CASPubMed Google Scholar
Nilsson, S. K. et al. Immunofluorescence characterization of key extracellular matrix proteins in murine bone marrow in situ. J. Histochem. Cytochem.46, 371–377 (1998). ArticleCASPubMed Google Scholar
Keating, A. et al. Donor origin of the in vitro haematopoietic microenvironment after marrow transplantation in man. Nature298, 280–283 (1982). ArticleCASPubMed Google Scholar
Cooper, A. R. & MacQueen, H. A. Subunits of laminin are differentially synthesized in mouse eggs and early embryos. Dev. Biol.96, 467–471 (1983). ArticleCASPubMed Google Scholar
Waller, E. K., Huang, S. & Terstappen, L. Changes in the growth properties of CD34+, CD38− bone marrow progenitors during human fetal development. Blood86, 710–718 (1995). CASPubMed Google Scholar
Simmons, P. J. & Torok-Storb, B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood78, 55–62 (1991). CASPubMed Google Scholar
Keating, A., Whalen, C. K. & Singer, J. W. Cultured marrow stromal cells express common acute lymphoblastic leukaemia antigen (CALLA): implications for marrow transplantation. Br. J. Haematol.55, 623–628 (1983). ArticleCASPubMed Google Scholar
Dennis, J. E. & Charbord, P. Origin and differentiation of human and murine stroma. Stem Cells20, 205–214 (2002). ArticleCASPubMed Google Scholar
Mythreye, K. & Blobe, G. C. Proteoglycan signaling co-receptors: roles in cell adhesion, migration and invasion. Cell. Signal.21, 1548–1558 (2009). ArticleCASPubMedPubMed Central Google Scholar
Friedenstein, A. J., Petrakova, K. V., Kurolesova, A. I. & Frolova, G. P. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation6, 230–247 (1968). ArticleCASPubMed Google Scholar
Horwitz, E. M. et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy7, 393–395 (2005). ArticleCASPubMed Google Scholar
Dominici, M. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy8, 315–317 (2006). ArticleCASPubMed Google Scholar
Uccelli, A., Moretta, L. & Pistoia, V. Mesenchymal stem cells in health and disease. Nature Rev. Immunol.8, 726–736 (2008). ArticleCAS Google Scholar
Bartholomew, A. et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol.30, 42–48 (2002). ArticlePubMed Google Scholar
Di Nicola, M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood99, 3838–3843 (2002). ArticleCASPubMed Google Scholar
Krampera, M. et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood101, 3722–3729 (2003). ArticleCASPubMed Google Scholar
Meisel, R. et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase-mediated tryptophan degradation. Blood103, 4619–4621 (2004). ArticleCASPubMed Google Scholar
Glennie, S., Soeiro, I., Dyson, P. J., Lam, E. W. & Dazzi, F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood105, 2821–2827 (2005). ArticleCASPubMed Google Scholar
Plumas, J. et al. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia19, 1597–1604 (2005). ArticleCASPubMed Google Scholar
Aggarwal, S. & Pittenger, M. F. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood105, 1815–1822 (2005). ArticleCASPubMed Google Scholar
Pabst, R. Plasticity and heterogeneity of lymphoid organs. What are the criteria to call a lymphoid organ primary, secondary or tertiary? Immunol. Lett.112, 1–8 (2007). ArticleCASPubMed Google Scholar
Sipkins, D. A. et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature435, 969–973 (2005). ArticleCASPubMedPubMed Central Google Scholar
Holmes, K., Roberts, O. L., Thomas, A. M. & Cross, M. J. Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell. Signal.19, 2003–2012 (2007). ArticleCASPubMed Google Scholar
Kopp, H. G., Hooper, A. T., Avecilla, S. T. & Rafii, S. Functional heterogeneity of the bone marrow vascular niche. Ann. NY Acad. Sci.1176, 47–54 (2009). ArticleCASPubMed Google Scholar
Kiel, M. J., Yilmaz, O. H., Iwashita, T., Terhorst, C. & Morrison, S. J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell121, 1109–1121 (2005). ArticleCASPubMed Google Scholar
Sapoznikov, A. et al. Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches. Nature Immunol.9, 388–395 (2008). ArticleCAS Google Scholar
Pereira, J. P., An, J., Xu, Y., Huang, Y. & Cyster, J. G. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nature Immunol.10, 403–411 (2009). ArticleCAS Google Scholar
Maeda, K., Kosco-Vilbois, M. H., Burton, G. F., Szakal, A. K. & Tew, J. G. Expression of the intercellular adhesion molecule-1 on high endothelial venules and on non-lymphoid antigen handling cells: interdigitating cells, antigen transporting cells and follicular dendritic cells. Cell Tissue Res.279, 47–54 (1995). ArticleCASPubMed Google Scholar
Szabo, M. C., Butcher, E. C. & McEvoy, L. M. Specialization of mucosal follicular dendritic cells revealed by mucosal addressin-cell adhesion molecule-1 display. J. Immunol.158, 5584–5588 (1997). CASPubMed Google Scholar
Balogh, P., Aydar, Y., Tew, J. G. & Szakal, A. K. Appearance and phenotype of murine follicular dendritic cells expressing VCAM-1. Anat. Rec.268, 160–168 (2002). ArticleCASPubMed Google Scholar
Allen, C. D. & Cyster, J. G. Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Semin. Immunol.20, 14–25 (2008). ArticleCASPubMedPubMed Central Google Scholar
Qin, D. et al. Fc gamma receptor IIB on follicular dendritic cells regulates the B cell recall response. J. Immunol.164, 6268–6275 (2000). ArticleCASPubMed Google Scholar
Cyster, J. G. et al. Follicular stromal cells and lymphocyte homing to follicles. Immunol. Rev.176, 181–193 (2000). ArticleCASPubMed Google Scholar
Kapasi, Z. F. et al. Follicular dendritic cell (FDC) precursors in primary lymphoid tissues. J. Immunol.160, 1078–1084 (1998). CASPubMed Google Scholar
Munoz-Fernandez, R. et al. Follicular dendritic cells are related to bone marrow stromal cell progenitors and to myofibroblasts. J. Immunol.177, 280–289 (2006). ArticleCASPubMed Google Scholar
Bachmann, M. F., Odermatt, B., Hengartner, H. & Zinkernagel, R. M. Induction of long-lived germinal centers associated with persisting antigen after viral infection. J. Exp. Med.183, 2259–2269 (1996). ArticleCASPubMed Google Scholar
Kundig, T. M. et al. On T cell memory: arguments for antigen dependence. Immunol. Rev.150, 63–90 (1996). ArticleCASPubMed Google Scholar
Katakai, T. et al. A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells. Int. Immunol.16, 1133–1142 (2004). ArticleCASPubMed Google Scholar
Sixt, M. et al. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity22, 19–29 (2005). ArticleCASPubMed Google Scholar
Luther, S. A., Tang, H. L., Hyman, P. L., Farr, A. G. & Cyster, J. G. Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. Proc. Natl Acad. Sci. USA.97, 12694–12699 (2000). ArticleCASPubMedPubMed Central Google Scholar
Okada, T. & Cyster, J. G. CC chemokine receptor 7 contributes to Gi-dependent T cell motility in the lymph node. J. Immunol.178, 2973–2978 (2007). ArticleCASPubMed Google Scholar
Link, A. et al. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nature Immunol.8, 1255–1265 (2007). This paper shows IL-7-expressing stromal cells in SLOs. ArticleCAS Google Scholar
Forster, R., Davalos-Misslitz, A. C. & Rot, A. CCR7 and its ligands: balancing immunity and tolerance. Nature Rev. Immunol.8, 362–371 (2008). ArticleCAS Google Scholar
Gretz, J. E., Kaldjian, E. P., Anderson, A. O. & Shaw, S. Sophisticated strategies for information encounter in the lymph node: the reticular network as a conduit of soluble information and a highway for cell traffic. J. Immunol.157, 495–499 (1996). CASPubMed Google Scholar
Balogh, P., Aydar, Y., Tew, J. G. & Szakal, A. K. Appearance and phenotype of murine follicular dendritic cells expressing VCAM-1. Anat. Rec.268, 160–168 (2002). ArticleCASPubMed Google Scholar
Roozendaal, R., Mebius, R. E. & Kraal, G. The conduit system of the lymph node. Int. Immunol.20, 1483–1487 (2008). ArticleCASPubMed Google Scholar
McCuskey, R. S. Morphological mechanisms for regulating blood flow through hepatic sinusoids. Liver20, 3–7 (2000). ArticleCASPubMed Google Scholar
Fliedner, T. M. et al. Bone marrow structure and its possible significance for hematopoietic cell renewal. Ann. NY Acad. Sci.459, 73–84 (1985). ArticleCASPubMed Google Scholar
Li, J., Huston, G. & Swain, S. L. IL-7 promotes the transition of CD4 effectors to persistent memory cells. J. Exp. Med.198, 1807–1815 (2003). ArticleCASPubMedPubMed Central Google Scholar
McKinstry, K. K. et al. Rapid default transition of CD4 T cell effectors to functional memory cells. J. Exp. Med.204, 2199–2211 (2007). ArticleCASPubMedPubMed Central Google Scholar
Surh, C. D. & Sprent, J. Homeostasis of naive and memory T cells. Immunity29, 848–862 (2008). ArticleCASPubMed Google Scholar
Hargreaves, D. C. et al. A coordinated change in chemokine responsiveness guides plasma cell movements. J. Exp. Med.194, 45–56 (2001). ArticleCASPubMedPubMed Central Google Scholar
Hauser, A. E. et al. Chemotactic responsiveness toward ligands for CXCR3 and CXCR4 is regulated on plasma blasts during the time course of a memory immune response. J. Immunol.169, 1277–1282 (2002). ArticleCASPubMed Google Scholar
Mamani-Matsuda, M. et al. The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells. Blood111, 4653–4659 (2008). This study shows that memory B cells reside in the spleen. ArticleCASPubMed Google Scholar
Martinez-Gamboa, L. et al. Role of the spleen in peripheral memory B-cell homeostasis in patients with autoimmune thrombocytopenia purpura. Clin. Immunol.130, 199–212 (2009). ArticleCASPubMed Google Scholar
Dogan, I. et al. Multiple layers of B cell memory with different effector functions. Nature Immunol.10, 1292–1299 (2009). ArticleCAS Google Scholar
Nossal, G. J., Szenberg, A., Ada, G. L. & Austin, C. M. Single cell studies on 19s antibody production. J. Exp. Med.119, 485–502 (1964). ArticleCASPubMedPubMed Central Google Scholar
Cassese, G. et al. Inflamed kidneys of NZB / W mice are a major site for the homeostasis of plasma cells. Eur. J. Immunol.31, 2726–2732 (2001). ArticleCASPubMed Google Scholar
Benson, M. J. et al. The dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J. Immunol.180, 3655–3659 (2008). ArticleCASPubMed Google Scholar
Cassese, G. et al. Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J. Immunol.171, 1684–1690 (2003). ArticleCASPubMed Google Scholar
Seddon, B., Legname, G., Tomlinson, P. & Zamoyska, R. Long-term survival but impaired homeostatic proliferation of naive T cells in the absence of p56lck. Science290, 127–131 (2000). ArticleCASPubMed Google Scholar
Boyman, O., Letourneau, S., Krieg, C. & Sprent, J. Homeostatic proliferation and survival of naive and memory T cells. Eur. J. Immunol.39, 2088–2094 (2009). ArticleCASPubMed Google Scholar
Seddon, B., Tomlinson, P. & Zamoyska, R. Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nature Immunol.4, 680–686 (2003). ArticleCAS Google Scholar
Hataye, J., Moon, J. J., Khoruts, A., Reilly, C. & Jenkins, M. K. Naive and memory CD4+ T cell survival controlled by clonal abundance. Science312, 114–116 (2006). This paper shows that the pool size of memory CD4+ THcells is regulated by clonal abundance and suggests the existence of specific survival niches in the body. ArticleCASPubMed Google Scholar
Tomayko, M. M. et al. Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities. J. Immunol.181, 27–38 (2008). ArticleCASPubMed Google Scholar
Becker, T. C., Coley, S. M., Wherry, E. J. & Ahmed, R. Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells. J. Immunol.174, 1269–1273 (2005). ArticleCASPubMed Google Scholar
Mazo, I. B. et al. Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity22, 259–270 (2005). References 108 and 109 shows that memory CD8+ T cells preferentially reside in the bone marrow. ArticleCASPubMed Google Scholar
Haaijman, J. J., Schuit, H. R. & Hijmans, W. Immunoglobulin-containing cells in different lymphoid organs of the CBA mouse during its life-span. Immunology32, 427–434 (1977). CASPubMedPubMed Central Google Scholar
Terstappen, L. W., Johnsen, S., Segers-Nolten, I. M. & Loken, M. R. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood76, 1739–1747 (1990). CASPubMed Google Scholar
Jego, G. et al. Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells. Blood94, 701–712 (1999). CASPubMed Google Scholar
Sykes, M. & Nikolic, B. Treatment of severe autoimmune disease by stem-cell transplantation. Nature435, 620–627 (2005). ArticleCASPubMed Google Scholar
Alexander, T. et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood113, 214–223 (2009). ArticleCASPubMed Google Scholar
Podojil, J. R., Turley, D. M. & Miller, S. D. Therapeutic blockade of T-cell antigen receptor signal transduction and costimulation in autoimmune disease. Adv. Exp. Med. Biol.640, 234–251 (2008). ArticleCASPubMedPubMed Central Google Scholar