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. 1991 Mar 15;88(6):2151–2155. doi: 10.1073/pnas.88.6.2151

Receptor-stimulated death pathway is opened by antigen in mature T cells.

J H Russell 1, C L White 1, D Y Loh 1, P Meleedy-Rey 1
PMCID: PMC51187  PMID: 1826050

Abstract

Clonal deletion provides an important mechanism for the elimination of autoreactive T cells. Deletion is accomplished by programmed cell death directed by interaction of the T-cell receptor (TCR) of the developing thymocyte with major histocompatibility complex elements in the thymic environment. In this report we present evidence to support the hypothesis that the activation and the maturation state of the T cell may be important in coupling the TCR to the "death program." We show that coupling of the TCR to the death program is open during maturation but closed in naive mature T cells. However, during primary antigenic stimulation, coupling between the TCR and the death program is reopened, as demonstrated by the stimulation of the death of these cells by immobilized anti-TCR. Our results suggest that further examination of mature cells that are either resistant or sensitive to receptor-stimulated death may lead to the identification of the components of the death pathway and may provide clues to the regulation of their coupling to TCR signals.

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Selected References

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  1. Ashwell J. D., Cunningham R. E., Noguchi P. D., Hernandez D. Cell growth cycle block of T cell hybridomas upon activation with antigen. J Exp Med. 1987 Jan 1;165(1):173–194. doi: 10.1084/jem.165.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashwell J. D., Longo D. L., Bridges S. H. T-cell tumor elimination as a result of T-cell receptor-mediated activation. Science. 1987 Jul 3;237(4810):61–64. doi: 10.1126/science.3037698. [DOI] [PubMed] [Google Scholar]
  3. Bruce J., Symington F. W., McKearn T. J., Sprent J. A monoclonal antibody discriminating between subsets of T and B cells. J Immunol. 1981 Dec;127(6):2496–2501. [PubMed] [Google Scholar]
  4. Ceredig R., Lowenthal J. W., Nabholz M., MacDonald H. R. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Nature. 1985 Mar 7;314(6006):98–100. doi: 10.1038/314098a0. [DOI] [PubMed] [Google Scholar]
  5. Don M. M., Ablett G., Bishop C. J., Bundesen P. G., Donald K. J., Searle J., Kerr J. F. Death of cells by apoptosis following attachment of specifically allergized lymphocytes in vitro. Aust J Exp Biol Med Sci. 1977 Aug;55(4):407–417. doi: 10.1038/icb.1977.38. [DOI] [PubMed] [Google Scholar]
  6. Duke R. C., Chervenak R., Cohen J. J. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6361–6365. doi: 10.1073/pnas.80.20.6361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guidos C. J., Weissman I. L., Adkins B. Intrathymic maturation of murine T lymphocytes from CD8+ precursors. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7542–7546. doi: 10.1073/pnas.86.19.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  9. Kranz D. M., Sherman D. H., Sitkovsky M. V., Pasternack M. S., Eisen H. N. Immunoprecipitation of cell surface structures of cloned cytotoxic T lymphocytes by clone-specific antisera. Proc Natl Acad Sci U S A. 1984 Jan;81(2):573–577. doi: 10.1073/pnas.81.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  11. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Merćep M., Bluestone J. A., Noguchi P. D., Ashwell J. D. Inhibition of transformed T cell growth in vitro by monoclonal antibodies directed against distinct activating molecules. J Immunol. 1988 Jan 1;140(1):324–335. [PubMed] [Google Scholar]
  13. Merćep M., Noguchi P. D., Ashwell J. D. The cell cycle block and lysis of an activated T cell hybridoma are distinct processes with different Ca2+ requirements and sensitivity to cyclosporine A. J Immunol. 1989 Jun 1;142(11):4085–4092. [PubMed] [Google Scholar]
  14. Mueller D. L., Jenkins M. K., Schwartz R. H. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. doi: 10.1146/annurev.iy.07.040189.002305. [DOI] [PubMed] [Google Scholar]
  15. Nau G. J., Moldwin R. L., Lancki D. W., Kim D. K., Fitch F. W. Inhibition of IL 2-driven proliferation of murine T lymphocyte clones by supraoptimal levels of immobilized anti-T cell receptor monoclonal antibody. J Immunol. 1987 Jul 1;139(1):114–122. [PubMed] [Google Scholar]
  16. Penit C., Vasseur F., Papiernik M. In vivo dynamics of CD4-8- thymocytes. Proliferation, renewal and differentiation of different cell subsets studied by DNA biosynthetic labeling and surface antigen detection. Eur J Immunol. 1988 Sep;18(9):1343–1350. doi: 10.1002/eji.1830180907. [DOI] [PubMed] [Google Scholar]
  17. Penit C., Vasseur F. Sequential events in thymocyte differentiation and thymus regeneration revealed by a combination of bromodeoxyuridine DNA labeling and antimitotic drug treatment. J Immunol. 1988 May 15;140(10):3315–3323. [PubMed] [Google Scholar]
  18. Russell J. H., Dobos C. B. Characterization of a "heteroclitic" cytotoxic lymphocyte clone: heterogeneity of receptors or signals? J Immunol. 1983 Feb;130(2):538–541. [PubMed] [Google Scholar]
  19. Russell J. H. Internal disintegration model of cytotoxic lymphocyte-induced target damage. Immunol Rev. 1983;72:97–118. doi: 10.1111/j.1600-065x.1983.tb01074.x. [DOI] [PubMed] [Google Scholar]
  20. Russell J. H., Manning D. E., McCulley D. E., Meleedy-Rey P. Antigen as a positive and negative regulator of proliferation in cytotoxic lymphocytes. A model for the differential regulation of proliferation and lytic activity. J Immunol. 1988 Mar 15;140(6):1796–1801. [PubMed] [Google Scholar]
  21. Russell J. H., Meleedy-Rey P., McCulley D. E., Sha W. C., Nelson C. A., Loh D. Y. Evidence for CD8-independent T cell maturation in transgenic mice. J Immunol. 1990 May 1;144(9):3318–3325. [PubMed] [Google Scholar]
  22. Sanderson C. J. The mechanism of T cell mediated cytotoxicity. II. Morphological studies of cell death by time-lapse microcinematography. Proc R Soc Lond B Biol Sci. 1976 Jan 20;192(1107):241–255. doi: 10.1098/rspb.1976.0011. [DOI] [PubMed] [Google Scholar]
  23. Sha W. C., Nelson C. A., Newberry R. D., Kranz D. M., Russell J. H., Loh D. Y. Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature. 1988 Nov 3;336(6194):73–76. doi: 10.1038/336073a0. [DOI] [PubMed] [Google Scholar]
  24. Smith C. A., Williams G. T., Kingston R., Jenkinson E. J., Owen J. J. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. 1989 Jan 12;337(6203):181–184. doi: 10.1038/337181a0. [DOI] [PubMed] [Google Scholar]
  25. Teh H. S., Kisielow P., Scott B., Kishi H., Uematsu Y., Blüthmann H., von Boehmer H. Thymic major histocompatibility complex antigens and the alpha beta T-cell receptor determine the CD4/CD8 phenotype of T cells. Nature. 1988 Sep 15;335(6187):229–233. doi: 10.1038/335229a0. [DOI] [PubMed] [Google Scholar]
  26. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]

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