Abstract
Through the combined effects of positive and negative selection, T cell differentiation in the thymus generates a repertoire of mature T cells that is tailored to tolerate self antigens but mount strong responses to foreign antigens1,2. Thymic selection is associated with extensive cell death, and only a very small proportion of thymocytes are selected for survival and export to the extrathymic environment. This article provides an overview of thymic selection and the fate of thymocytes.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Sprent, J. T lymphocytes and the thymus. in: “Fundamental Immunology,” W. E. Paul, ed., Raven Press, New York (1993).
Jameson, S.C., K.A. Hogquist, and M.J. Bevan. Positive selection of thymocytes. Annu. Rev. Immunol. 13: 93 (1995).
Sprent, J., D. Lo, E.K. Gao, and Y. Ron. T cell selection in the thymus. Immunol. Rev. 101: 173 (1988).
Hogquist, K.A., S.C. Jameson, W.R. Heath, J.L. Howard, M.J. Bevan, and F.R. Carbone. T cell receptor antagonist peptides induce positive selection. Cell 76: 17 (1994).
Ashton-Rickardt, P.G., L. Van Kaer, T.N. Schumacher, H.L. Ploegh, and S. Tonegawa. Peptide contributes to the specificity of positive selection of CD8+ T cells in the thymus. Cell 73: 1041 (1993).
Sebzda, E., V.A. Wallace, J. Mayer, R.S. Yeung, T.W. Mak, and P.S. Ohashi. Positive and negative thymocyte selection induced by different concentrations of a single peptide. Science 263: 1615 (1994).
Ashton-Rickardt, P.G. and S. Tonegawa. A differential-avidity model for T-cell selection. Immunol. Today 15: 362 (1994).
Sprent, J. and S.R. Webb. Function and specificity of T cell subsets in the mouse. Adv. Immunol. 41: 39 (1987).
Scollay, R. and K. Shortman. Cell traffic in the adult thymus: Cell entry and exit, cell birth and death. in: “Recognition and Regulation in Cell Mediated Immunity,” J. D. Watson and J. Marbrook, eds., Dekker, New York (1985).
Surh, C.D. and J. Sprent. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372: 100 (1994).
Savill, J., V. Fadok, P. Henson, and C. Haslett. Phagocyte recognition of cells undergoing apoptosis. Immunol. Today 14: 131 (1993).
Kappler, J.W., N. Roehm, and P. Marrack. T cell tolerance by clonal elimination in the thymus. Cell 49: 273 (1987).
Fowlkes, B.J. and F. Ramsdell. T-cell tolerance. Curr. Opin. Immunol. 5: 873 (1993).
Nossal, G.J.V. Negative selection of lymphocytes. Cell 76: 229 (1994).
Sprent, J. Central tolerance of T cells. Internat. Rev. Immunol. 13: 95 (1995).
Marrack, P., L. Ignatowicz, J.W. Kappler, J. Boymel, and J.H. Freed. Comparison of peptides bound to spleen and thymus class II. J. Exp. Med. 178: 2173 (1994).
Sprent, J. and S.R. Webb. Intrathymic and extrathymic clonal deletion of T cells. Curr. Opin. Immunol. 7: 196 (1995).
Matzinger, P. and S. Guerder. Does T-cell tolerance require a dedicated antigen-presenting cell? Nature 338: 74 (1989).
Murphy, K.M., A.B. Heimberger, and D.H. Loh. Induction by antigen of intrathymic apoptosis of CD4+ CD8+TCRIO thymocytes in vivo. Science 250: 1720 (1990).
Schwartz, R.H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB 1 in interleukin-2 production and immunotherapy. Cell 71: 1065 (1992).
Janeway, C.A. and K. Bottomly. Signals and signs for lymphocyte responses. Cell76: 275 (1994).
Linsley, P.S. and J.A. Ledbetter. The role of the CD28 receptor during T cell responses to antigen. Annu. Rev. Immunol. 11: 191 (1993).
Liu, Y., B. Jones, W. Brady, and C.A. Janeway,Jr. Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat-stable antigen. Eur. J. Immunol. 22: 2855 (1992).
Dubey, C., M. Croft, and S.L. Swain. Costimulatory requirements of naive CD4+ T cells: ICAM-1 or B7–1 can stimulate naive CD4 T cell activation but both are required for optimal responses. J. Immunol. 155: 45 (1995).
Punt, J.A., B.A. Osborne, Y. Takahama, S.O. Sharrow, and A. Singer. 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. 179: 709 (1994).
Page, D.M., L.P. Kane, J.P. Allison, and S.M. Hedrick. Two signals are required for negative selection of CD4+CD8+ thymocytes. J. lmmunol. 151: 1868 (1993).
Aiba, Y., O. Mazda, M.M. Davis, S. Muramatsu, and Y. Katsura. Requirement of a second signal from antigen presenting cells in the clonal deletion of immature T cells. Internat. Immunol. 6: 1475 (1994).
Iwawabuchi, K., K.I. Nakayama, R.L. McCoy, F. Wang, T. Nishimura, S. Habu, K.W. Murphy, and D.Y. Loh. Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes. Proc. Natl. Acad. Sci. USA 89: 9000 (1992).
Shahinian, A., K. Pfeffer, K.P. Lee, T.M. Kundig, K. Kishihara, A. Wakeham, K. Kawai, P.S. Ohashi, C.B. Thompson, and T.W. Mak. Differential T cell costimulatory requirements in CD28-deficient mice. Science 261: 609 (1993).
Sha, W.C., C.A. Nelson, R.D. Newberry, D.M. Kranz, J.H. Russell, and D.Y. Loh. Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature 335: 271 (1988).
Sha, W.C., C.A. Nelson, R.D. Newberry, J.K. Pullen, L.R. Pease, J.H. Russell, and D.Y. Loh. Positive selection of transgenic receptor-bearing thymocytes by Kb antigen is altered by Kb mutations that involve peptide binding. Proc. Natl. Acad. Sci. USA 87: 6186 (1990).
Udaka, K., T.J. Tsomides, and H.N. Eisen. A naturally occurring peptide recognized by alloreactive CD8+ cytotoxic T lymphocytes in association with a class I MHC protein. Cell 69: 989 (1992).
Sykulev, Y., A. Brunmark, M. Jackson, R.J. Cohen, P.A. Peterson, and H.N. Eisen. Kinetics and affinity of reactions between an antigen-specific T cell receptor and peptide-MHC complexes. Immunity 1:15 (1994).
Sykulev, Y., A. Brunmark, T.J. Tsomides, S. Kageyama, M. Jackson, P.A. Peterson, and H.N. Eisen. High-affinity reactions between antigen-specific T-cell receptors and peptides associated with allogeneic and syngeneic major histocompatibility complex class I proteins. Proc. Natl. Acad. Sci. USA 91: 11487 (1994).
Yang, Y., K. Fruh, J. Chambers, J.B. Waters, L. Wu, T. Spies, and P.A. Peterson. Major histocompatibility complex (MHC)-encoded HAM2 is necessary for antigenic peptide loading onto class I MHC molecules. J. Biol. Chem. 267: 11669 (1992).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer Science+Business Media New York
About this chapter
Cite this chapter
Sprent, J. et al. (1996). The Thymus and T Cell Death. In: Gupta, S., Cohen, J.J. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VI. Advances in Experimental Medicine and Biology, vol 406. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0274-0_20
Download citation
DOI: https://doi.org/10.1007/978-1-4899-0274-0_20
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-0276-4
Online ISBN: 978-1-4899-0274-0
eBook Packages: Springer Book Archive