The thymus and negative selection

Springer Science and Business Media LLC - Tập 21 - Trang 315-323 - 2000
Hidehiro Kishimoto1, Jonathan Sprent1
1Department of Immunology, IMM4, The Scripps Research Institute, La Jolla

Tóm tắt

Self-tolerance induction is largely a reflection of negative selection (deletion) of autoreactive T cells in the thymus. Evidence is presented that negative selection occurs at a relatively late stage of thymocytes differentiation and affects a population of semimature HSAhi CD4+8− cells found in the medulla. Negative selection involves a number of cell-surface molecules on T cells, including Fas, CD28, CD5, and CD43. These molecules appear to act in consort, thereby ensuring that negative selection is highly efficient.

Tài liệu tham khảo

Robey E, Fowlkes BJ: Selective events in T cell development. Annu Rev Immunol 1994;12:675–705. Nossal GJV: Negative selection of lymphocytes. Cell 1994;76:229–239. Sprent J: Central tolerance of T cells. Int Rev Immunol 1995;13:95–105. Fink PJ, Bevan MJ: Positive selection of thymocytes. Adv Immunol 1995;59:99–133. Amsen D, Kruisbeek AM: Thymocyte selection: not by TCR alone. Immunol Rev 1998;165:209–229. Viret C, Wong FS, Janeway CAJ Jr: Designing and maintaining the mature TCR repertoire: the continuum of self-peptide: self-MHC complex recognition. Immunity 1999;10:559–568. Ernst B, Lee D-S, Chang J, et al. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 1999;11:173–181. Goldrath AW, Bevan MJ: Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 1999;11:183–190. Shi Y, Bissomete RP, Parfrey N, et al.: In vivo administration of antibodies to the CD3-T cell receptor complex induces cell death (apoptosis) in immature thymocytes. J Immunol 1991;146:3340–3346. Murphy KM, Heimberger AB, Loh DH: Induction by antigen of intrathymic apoptosis of CD4+ CD8+ TCR1 thymocytes in vivo. Science 1990;250:1720–1723. Jondal M, Okret S, McConkey D: Killing of immature CD4+ CD8+ thymocytes in vivo by anti-CD3 or 5′ (N-ethyl)-carboxamide-adenosine is blocked by glucocorticoid receptor antagonist RU-486. Eur J Immunol 1993;23:1246–1250. Xue Y, Murdjeva M, Okret S, et al.: Inhibition of 1-Ad-, but not Db-restricted peptide-induced thymic apoptosis by glucocorticoid receptor antagonist RU486 in T cell receptor transgenic mice. Eur J Immunol 1996;26:428–434. Martin S, Bevan MJ: Antigen-specific and nonspecific deletion of immature cortical thymocytes caused by antigen injection. Eur J Immunol 1997;27:2726–2736. von Boehmer H: Developmental biology of T cells in T cell receptor transgenic mice. Annu Rev Immunol 1990;8:531–556. Laufer TM, Climcher LH, Lo D: Using thymus anatomy to dissect T cell repertoire selection. Semin Immunol 1999;11:65–70. Page DM, Kane LP, Allison JP, et al.: Two signals are required for negative selection of CD4+CD8+ thymocytes. J Immunol 1993;151:1868–1880. Punt JA, Osbome BA, Takahama Y, et al.: Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28. J Exp Med 1994;179:709–713. Aiba Y, Mazda O, Davis MM, et al.: Requirement of a second signal from antigen presenting cells in the clonal deletion of immature T cells. Int J Immunol 1994;6:1475–1483. Kishimoto H, Sprent J: Negative selection in the thymus includes semi-mature T cells. J Exp Med 1997;185:263–272. Kishimoto H, Sprent J: Strong TCR ligation without costimulation causes rapid onset of Fas-dependent apoptosis of naive murine CD4+ T cells. J Immunol 1999;163:1817–1826. Green DR, Scott DW: Activation-induced apoptosis in lymphocytes. Curr Opin Immunol 1994;6:476–487. Nagata S, Golstein P: The Fas death factor. Science 1995;267:1449–1456. Marrack P, Kappler JW: The staphylococcalentero toxins and their relatives. Science 1990;248:704–711. Kishimoto H, Surh CD, Sprent J: A role for Fas in negative selection of thymocytes in vivo. J Exp Med 1998;187:1427–1438. Theofilopoulos AN: The basis of autoimmunity: Part I. Mechanisms of aberrant self-recognition. Immunol Today 1995;16:90–98. Shahinian A, Pfeffer K, Lee KP, et al.: Differential T cell costimulatory requirements in CD28-deficient mice. Science 1993;261:609–612. Kishimoto H, Sprent J: Several different cell-surface molecules control negative selection of medullary thymocytes. J Exp Med 1999;190:65–73. Punt JA, Havran W, Abe R, et al.: T cell receptor (TCR)-induced death of immature CD4+ CD8+ thymocytes by two distinct mechanisms differing in their requirement for CD28 costimulation: implications for negative selection in the thymus. J Exp Med 1997;186:1911–1922. Page DM: Thymic selection and autoreactivity are regulated by multiple coreceptors involved in T cell activation. J Immunol 1999; 163:3577–3581. van Oers NSC: T cell receptor-mediated signs and signals governing T cell development. Semin Immunol 1999;11:227–237. Mariathason S, Jones RG, Ohashi PS: Signals involved in thymo-