Immune Tolerance and the Nervous System
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 490)
The immune system exists to protect the body from infection by a plethora of microorganisms, including bacteria, viruses, and parasites. This is accomplished by a variety of interdependent methods. The skin is an often overlooked but extremely effective barrier to infection, and is one of several innate mechanisms of immunity. NK cells, which appear to primarily recognize changes in the levels of major histocompatability complex class I (MHC cl) molecules expressed on cells within the body, represent another form of innate immunity. They represent a form of innate immunity because while they can protect the body against tumor cells or virally-infected cells, which often have altered levels of MHC cI expression, they have no “memory” of a given prior viral infection or particular type of tumor. This contrasts with T cells and B cells which comprise the specific immune response. A given T cell or B cell and its clonal progeny are all specific for a given foreign microbial antigen, and furthermore, can “remember” a prior encounter with that antigen and effectively remove it much more quickly upon secondary exposure to the antigen. This phenomena is the basis for vaccination. Thus, after vaccination with exposure to antigens from a particular virus or bacterium with adjuvant, there is activation and expansion of T cells and B cells with specific receptors for those particular antigens. If some years later the same individual is exposed to the infectious virus or bacteria, the T cells and B cells which have been previously activated and expanded will be mobilized very quickly and in most cases eliminate the infectious agent before it can do any harm to the body.
KeywordsExperimental Autoimmune Encephalomyelitis Myelin Basic Protein Negative Selection Experimental Allergic Encephalomyelitis Cell Tolerance
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Markowitz, J., H. J. Auchincloss, M. Gursby, et al. 1993. Class II-positive hematopoietic cells cannot mediate positive selection of CD4+ T lymphocytes in class II-deficient mice. Proc. Natl. Acad. Sci. USA
Laufer, T., J. DeKoning, J. Markowitz, et al. 1996. Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature
Lauter, T.M., L. Fan, and L.H. Glimcher. 1999. Self-reactive T cells selected on thymic cortical epithelium are polyclonal and are pathogenic in vivo. J. Immunol.
Surh, C. and J. Sprent. 1994. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature
Oukka, M., E. Colucci-Guyon, P. Tran et al. 1996. CD4 T cell tolerance to nuclear proteins induced by medullary thymic epithelium. Immunity
Evavold, B. D. and P. M. Allen. 1991. Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science
Allen, P. 1994. Peptides in positive and negative selection: a delicate balance. Cell
Vidal, K., B. Hsu, C. Williams et al. 1996. Endogenous altered peptide ligands can affect peripheral T cell responses. J. Exp. Med.
Bevan, M. 1997. In thymic selection, peptide diversity gives and takes away. Immunity
Ignatowicz, L., J. Kappler and P. Marrack. 1996. The repertoire of T cells shaped by a single MHC/peptide ligand. Cell
Grubin, C., S. Kovats, P. deRoos et al. 1997. Deficient positive selection of CD4 T cells in mice displaying altered repertoires of MHC class II-bound self-peptides. Immunity
Surh, C., D. Lee, W. Fung-Leung et al. 1997. Thymic selection by a single MHC/peptide ligand produces a semidiverse repertoire of CD4+ T cells. Immunity
Ashton-Rickardt, P. G., A. Bandeira, J. R. Delaney et al. 1994. Evidence for a differential avidity model of T cell selection in the thymus. Cell
Girao, C., Q. Hu, J. Sun et al. 1997. Limits to the differential avidity model of T cell selection in the thymus. J Immunol.
Hogquist, K. A., S. C. Jameson, W. R. Health et al. 1994. T cell receptor antagonist peptides induce positive selection. Cell
Hogquist, K., S. Jameson and M. Bevan. 1995. Strong agonist ligands for the T cell receptor do not mediate positive selection of functional CD8+ T cells. Immunity
Sebzda, E., V. Wallace, J. Mayer et al. 1994. Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science
Cook, J., E. Wormstall, T. Hornell et al. 1997. Quantitation of the cell surface level of Ld resulting in positive versus negative selection of the 2C transgenic T cell receptor in vivo. Immunity
Alam, S., P. Travers, J. Wung et al. 1996. T-cell-receptor affinity and thymocyte positive selection. Nature
Langman, R. and M. Cohn. 1996. Terra Firma: A retreat from danger. J. Immunol.
Cohen, J. 1993. Apoptosis. Immunol. Today
Le, P., H. Maecher and J. Cook. 1995. In situ detection and characterization of apototic thymocytes in human thymus. Expression of bcl-2 in vivo
does not prevent apoptosis. J. Immunol.
Liu, G., P. Farichild, R. Smith et al. 1995. Low avidity recognition of self-antigen by T cells permits escape from central tolerance. Immunity
Kanagawa, O., S. Martin, B. Vaupel et al. 1998. Autoreactivity of T cells from nonobese diabetic mice: an I-Ag7-dependent reaction. Proc. Natl. Acad. Sci. USA
Ridgway, W.M., Fasso, M. and Fathman, C.G. 1999. A new look at MHC and autoimmune disease. Science
Ota, K., M. Matsui, E. Milford et al. 1990. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature
346: 183.PubMedCrossRefGoogle Scholar
Scholz, C., K. Patton, D. Anderson et al. 1998. Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. J. Immunol.
Zhang, J., S. Markovic, J. Raus et al. 1994. Increased frequency of IL-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.
Lovett-Racke, A., J. Trotter, J. Lauber.et al. 1998. Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients.J. Clin. Invest.
Lovett-Racke, A., J.
Lauber. et al. 1998. Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. J. Clin. Invest.
Lenschow, D. and J.A. Bluestone. 1996. CD28/B7 system of T cell costimulation. Ann. Rev. Immunol.
Tivol, E., A.N. Schweitzer, and A.H. Sharpe. 1996. Costimulation and autoimmunity. Curr. Opin. Immunol.
Linsley, P. 1995. Distinct roles for CD28 and cytotoxic T lymphocyte-associated molecule-4 receptors during T cell activation? J. Exp. Med.
Thompson, C.B., and Allison, J.P. 1997. The emerging role of CTLA-4 as an immune attenuator. Immunity
Jenkins, M. K., D. M. Pardoll, J. Mizuguchi et al. 1987. T-cell unresponsiveness in vivo
and in vitro
: fine specificity of induction and molecular characterization of the unresponsive state. Immunological Reviews
Karpus, W., J. Pope, J. Peterson et al. 1995. Inhibition of Theiler’s virus-mediated demyelination by peripheral immune tolerance induction. J. Immunol.
Kennedy, K., W. Smith, S. Miller et al. 1997. Induction of antigen-specific tolerance for the treatment of ongoing, relapsing autoimmune encephalomyelitis: a comparison between oral and peripheral tolerance. J. Immunol.
Vandenbark, A., B. Celnik, M. Vainiene et al. 1995. Myelin antigen-coupled splenocytes suppress experimental autoimmune encephalomyelitis in Lewis rats through a partially reversible energy mechanism. J. Immunol.
Boussiotis, V., D. Barber, T. Nakaria et al. 1994. Prevention of T cell energy by signaling through the gamma c chain of the IL-2 receptor. Science
Linsley, P. S., P. M. Wallace, J. Johnson et al. 1992. Immunosuppression in vivo
by a soluble form of the CTLA-4 T cell activation molecule. Science
Milich, D., M. Chen, J. Hughes et al. 1998. The secreted hepatitis B precore antigen can modulate the immune response to the nucleocapsid: a mechanism for persistence. J. Immunol.
Wallace, P., J. Rodgers, G. Leytze et al. 1995. Induction and reversal of long-lived specific unresponsiveness to a T-dependent antigen following CTLA4Ig treatment. J. Immunol.
Finck, B., P. Linsley and D. Wofsy. 1994. Treatment of murine lupus with CTLA4Ig. Science
Arima, T., A. Rehman, W. Hickey et al. 1996. Inhibition by CTLA4Ig of experimental allergic encephalomyelitis. J Immunol.
Lenschow, D. J., Y. Zeng, J. R. Thistlethwaite et al. 1992. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA41g. Science
Larsen, C., E. Elwood, D. Alexander et al. 1996. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature
Kirk, A., D. Harlan, N. Armstrong et al. 1997. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc. Natl. Acad. Sci USA
Balasa, B., T. Krahl, G. Patstone et al. (1997). CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J. Immunol.
Critchfield, J., M. Racke, J. Zuniga-Pflucker et al. 1994. T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis. Science
263: 1139.PubMedCrossRefGoogle Scholar
Van Parijs, L., A. Biuckians, A. Ibragimov et al. 1997. Functional responses and apoptosis of CD25 (IL-2R alpha)-deficient T cells expressing a transgenic antigen receptor. J Immunol.
Noel, P., L. Biose and C. Thompson. 1996. CD28 costimulation prevents cell death during primary T cell activation. J. Immunol.
Boise, L., A. Minn, P. Noel et al. 1995. CD28 costimulation can promote T cell survival by enhancing the expression of Bel-XL. Immunity
Mueller, D., S. Seiffert, W. Fang et al. 1996. Differential regulation of bc1–2 and bel-x by CD3, CD28, and the IL-2 receptor in cloned CD4+ helper T cells. A model for the long-term survival of memory cells. J Immunol.
Radvanyi, L., Y. Shi, H. Vaziri et al. 1996. CD28 costimulation inhibits TCR-induced apoptosis during a primary T cell response. J. Immunol.
Nakajima, H. and W. Leonard. 1997. Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain: defective Fas ligand expression in gamma-chain-deficient mice. J. Immunol.
Brunner, T., R. Mogil, D. LaFace et al. 1995. Cell-autonomous Fas (CD95) /Fas ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature
Dhein, J., H. Walczak, C. Baumler et al. 1995. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature
Ju, S., D. Panka, H. Cut et al. 1995. Fas (CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature
Ettinger, R., J. Wang, P. Bossu et al. 1994. Functional distinctions between MRL-1pr and MRL-gld lymphocytes. Normal cells reverse the gld but not 1pr immunoregulatory defect. J. Immunol.
Nagata, S. and P. Golstein. 1995. The Fas death factor. Science
Streilein, J. 1996. Unraveling immune privilege. Science
Streilein, J., B. Ksander and A. Taylor. 1997. Immune deviation in relation to ocular immune privilege. J. Immunol.
Griffith, T., T. Brunner, S. Fletcher et al. 1996. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science
Vella, A., J. McCormack, P. Linsley et al. 1995. Lipopolysaccharide interferes with the induction of peripheral T cell death. Immunity
Pape, K., A. Khoruts, A. Mondino et al. 1997. Inflammatory cytokines enhance the in vivo
clonal expansion and differentiation of antigen-activated CD4+ T cells. J Immunol.
Abbas, A., K. Murphy and A. Sher. 1996. Functional diversity of helper T lymphocytes. Nature
O’Garra, A. (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity
8, 275–283.PubMedCrossRefGoogle Scholar
Fiorentino, D., A. Zlotnik, T. Mosmann et al. 1991. IL-I0 inhibits cytokine production by activated macrophages. J. Immunol.
Wang, P., P. Wu, M. Siegel et al. 1994. IL-10 inhibits transcription of cytokine genes in human peripheral blood mononuclear cells. J Immunol.
Powrie, F., S. Menon and R. Coffman. 1993. Interleukin-4 and interleukin-10 synergize to inhibit cell-mediated immunity in vivo.
Eur. J. Immunol.
Pajkrt, D., L. Camoglio, M. Tiel-van Buul et al. 1997. Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration. J. Immunol. 158:3971.
Bright, J., L. Kerr and S. Sriram. 1997. TGF-beta inhibits IL-2-induced tyrosine phosphorylation and activation of Jak-1 and Stat 5 in T lymphocytes. J. Immunol.
Chen, Y., J. Inobe and H. Weiner. 1995. Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediated active suppression. J. Immunol.
Weiner, H. 1997. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol. Today
Khoury, S. J., W. W. Hancock and H. L. Weiner. 1992. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with down-regulation of inflammatory cytokines and differential upregulation of TGF-D, IL-4 and PGE expression in the brain. J. Exp. Med.
Fukaura, H., S. Kent, M. Pietrusewicz et al. 1996. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-01-secreting Th3 T cells by oral administration of myelin in multiple sclerosis. J. Clin. Invest.
Nicholson, L. and V. Kuchroo. 1996. Manipulation of the Thl/Th2 balance in autoimmune disease. Curr. Opin. Immunol.
Khoruts, A., S. Miller and M. Jenkins. 1995. Neuroantigen-specific Th2 cells are inefficient suppressors of experimental autoimmune encephalomyelitis induced by effector Thl cells. J Immunol.
Cua, D., D. Hinton and S. Stohlman. 1995. Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease. J. Immunol.
Falcone, M. and B. Bloom. 1997. A T helper cell 2 (Th2) immune response against non-self antigens modifies the cytokine profile of autoimmune T cells and protects against experimental allergic encephalomyelitis. J. Exp. Med.
Racke, M., A. Bonomo, D. Scott et al. 1994. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J. Exp. Med.
Shaw, M., J. Lorans, A. Dhawan et al. 1997. Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis. J. Exp. Med.
Mathisen, P., M. Yu, J. Johnson et al. 1997. Treatment of experimental autoimmune encephalomyelitis with genetically modified memory T cells. J. Exp. Med.
Williams, K. and W. Hickey. 1995. Traffic of hematogenous cells through the central nervous system. Curr. Top. Microbiol. Immunol.
Akkaraju, S., W. Ho, D. Leong et al. 1997. A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis. Immunity
Ferber, I., G. Schcnrich, J. Schenkel et al. 1994. Levels of peripheral T cell tolerance induced by different doses of tolerogen. Science
Rocha, B., A. Grandien and A. Freitas. 1995. Anergy and exhaustion are independent mechanisms of peripheral T cell tolerance. J. Exp. Med.
Weissman, I. 1994. Developmental switches in the immune system. Cell
Melamed, D. and D. Nemazee. 1997. Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest. Proc. Natl. Acad. Sci. USA
Melamed, D., R. Benschop, J. Cambier et al. 1998. Developmental regulation of f3 lymphocyte immune tolerance compartmentalized clonal selection from receptor selection. Cell
Lang, J., B. Arnold, G. Hammerling et al. 1997. Enforced Bc1–2 expression inhibits antigen-mediated clonal elimination of peripheral B cells in an antigen dose-dependent manner and promotes receptor editing in autoreactive, immature B cells. J. Exp. Med.
Nemazzee, D. and K. Burki. 1989. Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. Nature
Nossal, G. and B. Pike. 1980. Clonal energy: persistence in tolerant mice of antigen-binding B lymphocytes incapable of responding to antigen or mitogen. Proc. Natl. Acad. Sci. USA 77:1602.
Goodnow, C. C. 1992. Transgenic mice and analysis of B-cell tolerance. Annual Review of Immunology
Fulcher, D. and A. Basten. 1994. Reduced life span of anergic self-reactive B cells in a double-transgenic model. J. Exp. Med.
Cyster, J., S. Hartley and C. Goodnow. 1994. Competition for follicular niches excludes self-reactive cells from the recirculating B-cell repertoire. Nature
Nikolic, B. and M. Sykes. 1997. Bone marrow chimerism and transplantation tolerance. Curr. Opin. Immunol.
Burt, R., W. Burns and S. Miller. 1997. Bone marrow transplantation for multiple sclerosis: returning to Pandora’s box. Immunol. Today
Fassas, A., A. Anagnostopoulos, A. Kazis et al. 1997. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Trans.
Krance, R. and M. Brenner. 1998. BMT beats autoimmune disease. Nature Med.
© Springer Science+Business Media New York 2001