Abstract
The accurate discrimination of the immune system between pathogens and self-determinants is based on specific recognition events by receptors on B and T lymphocytes. The enormous diversity of the receptor repertoire is achieved by random rearrangement of DNA segments. In this process specificities for non-self as well as for self-determinants are created. T lymphocytes with high affinity for self-antigens are physically eliminated when they develop in the thymus provided the respective self-antigen is present on bone marrow derived cells (von Boehmer, 1990). Clonal deletion appears to be highly sensitive. Even thymocytes with an avidity below the required threshold for activation in the periphery are deleted (Pircher et al., 1991; Knobloch et al., 1992). On the other hand, thymocytes are not deleted but rendered functionally incompetent (clonal anergy) when the self-antigens are exclusively expressed on thymic epithelial cells (Ramsdell et al., 1989; Salaun et al., 1990; Hoffmann et al., 1992; Schönrich et al., 1992a).
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References
Adams, T.E., Alpert, S. and Hanahan, D.(1987)Non-tolerance and autoantibodies to a transgenic self antigen expressed in pancreatic b cells. Nature 325: 223–228
Arnold, B., Dill, O., Küblbeck, G., Jatsch, L., Simon, M.M., Tucker, J. and Hämmerling, G.J.(1988)Alloreactive immune responses of transgenic mice expressing the foreign transplantation antigen in a soluble form. Proc Natl Acad Sei USA 85: 2269–2273
Arnold, B., Schönrich, G. and Hämmerling, G.J.(1993)Multiple levels of peripheral tolerance. Immunol Today 14: 12–14
Auphan, N., Jézo-Brémond, A., Schönrich, G., Hämmerling, G.J., Arnold, B., Malissen, B. and Schmitt-Verhulst, A.-M.(1992)Threshold tolerance in H-2Kb-specific TCR transgenic mice expressing mutant H-2Kb: helper-dependent CTL. Int.Immunol 4, 12: 1419–1428
Ciliberto, G., Arcone, R., Wagner, E.F. and Rüther, U.(1987)Inducible and tissue-specific expression of human C-reactive protein in transgenic mice. EMBO J 6, 13: 4017–4022
Fowlkes, B J. and Pardoll, D.M.(1989)Molecular and cellular events of T cell development. Adv Immunol 44: 207–264
Hämmerling, G.J., Schönrich, G., Momburg, F., Auphan, N., Malissen, M., Malissen, B., Schmitt-Verhulst, A.-M. and Arnold, B.(1991)Non-deletional mechanisms of peripheral and central tolerance: studies with transgenic mice with tissue specific expression of a foreign MHC class I antigen. Immunol Rev 122: 47–67
Heath, W.R., Allison, J., Hoffmann, M.W., Schonrich, G., Hammerling, G.J., Arnold, B. and Miller, J.F.A.P.(1992)Autoimmune diabetes as a consequence of locally produced interleukin-2. Nature 359: 547–549
Hoffmann, M.W., Allison, J. and Miller, J.F.A.P.(1992)Tolerance induction by thymic medullary epithelium. Proc Natl Acad Sci USA 89: 2526–2530
Hue, I.., Trucy, J., McCoy, C., Couez, D., Malissen, B. and Malissen, M.(1990)A novel type of aberrant T cell receptor alpha-chain gene rearrangement. Implications for allelic exclusion and the V-J recombination process. J Immunol 144: 4410–4419
Husbands, S.D., Schonrich, G., Arnold, B., Chandler, P.R., Simpson, E., Philpott, K.L., Tomlinsou, P., O’Reilly, L., Cooke, A. and Mellor, A.L.(1992)Expression of major histocompatibility complex class I antigens at low levels in the thymus induces T cell tolerance via a non-deletional mechanism involving downmodulation of CD8 and T cell receptor. Eur J Immunol 22: 2655–2661
Knobloch, M., Schonrich, G., Schenkel, J., Malissen, M., Malissen, B., Schmitt-Verhulst, A.-M., Hammerling, G.J. and Arnold, B.(1992)T cell activation and thymic tolerance induction require different adhesion intensities of the CD8 coreceptor. Int. Immunol 4: 1169–1174
Lo, D., Freedman, J., Hesse, S., Palmiter, R.D., Brinster, R.L. and Sherman, L.A.(1992)Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects both CD4+ and CD8+ T cells. Eur J Immunol 22: 1013–1022
Miller, J.F.A.P. and Morahan, G.(1992)Peripheral T cell tolerance. Annu Rev Immunol 10: 51–69
Morahan, G., Allison, J. and Miller, J.F.A.P.(1989)Tolerance of class I histocompatibility antigens expressed extrathymically. Nature 339: 622–624
Ohashi, P.S., Oehen, S., Buerki, K., Pircher, H., Ohashi, C.T., Odermatt, B., Malissen, B., Zinkernagel, R.M. and Hengartner, H. (1991) Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65: 305–317
Oldstone, M.B., Nerenberg, M., Southern, P., Price, J. and Lewicki, H.(1991)Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65: 319–331
Pircher, H., Hoffmann Rohrer, U., Moskophidis, D., Zinkernagel, R.M. and Hengartner, H.(1991)Lower receptor avidity required for thymic clonal deletion than for effector Tcell function. Nature 351: 482–485
Ramsdell, F., Lantz, T. and Fowlkes, B.J.(1989)A nondeletional mechanism of thymic self tolerance. Science 246: 1038–1041
Salaiin, J., Bandeira, A., Khazaal, I., Caiman, F., Coltey, M., Coutinho, A. and Le Douarin, N.M.(1990)Thymic epithelium tolerizes for histocompatibility antigens. Science 247: 1471–1475
Schonrich, G., Kalinke, U., Momburg, F., Malissen, M., Schmitt-Verhulst, A., Malissen, B., Hammerling, G.J. and Arnold, B.(1991)Downregulation of Tcell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction. Cell 65: 293–304
Schonrich, G., Momburg, F., Hammerling, G.J. and Arnold, B.(1992a)Anergy induced by thymic medullary epithelium. Eur J Immunol 22: 1687–1691
Schonrich, G., Momburg, F., Malissen, M., Schmitt-Verhulst, A.-M., Malissen, B., Hammerling, G.J. and Arnold, B.(1992b)Distinct mechanisms of extrathymic T cell tolerance due to differential expression of self-antigen. IntJmmunol 4, 5: 581–590
von Boehmer, H.(1990)Developmental biology of T cells in T cell-receptor transgenic mice. Ann Rev Immunol 8: 531–556
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© 1994 Springer-Verlag Berlin Heidelberg
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Arnold, B., Schönrich, G., Ferber, I., Alferink, J., Hämmerling, G.J. (1994). Tolerance induction in mature peripheral T cells. In: Zouali, M. (eds) Autoimmunity: Experimental Aspects. NATO ASI Series, vol 80. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78779-9_1
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