Abstract
EFFECTOR T cells are restricted to recognizing antigens associated with major histocompatibility complex (MHC) molecules1. Specific recognition is mediated by the αβ heterodimer of the T-cell receptor (TCR)/CD3 complex2,3, although other membrane components are involved in T-cell antigen recognition and functions. There has been much controversy in this regard over the part played by the CD4 glycoprotein. It is known that expression of CD4 correlates closely with the cell's ability to recognize antigens bound to class II MHC molecules4,5 and that CD4 can bind to class II molecules6. Also monoclonal antibodies to CD4 can modify signals generated through the TCR/CD3 complex7–10. It has therefore been proposed that CD4 binds to class II molecules, coaggregates with the TCR–CD3 complex and aids the activation of T cells. But given that TCR can itself impart restriction on the cell, it remains unclear whether the contribution of CD4-derived signals to those generated through the TCRaαβ–CD3 complex is central to this activation. Here we report that when preceded by ligation of CD4, signalling through TCRαβ results in T cell unresponsiveness due to the induction of activation dependent cell death by apoptosis. These results imply that CD4 is critically involved in determining the outcome of signals generated through TCR, and could explain why the induction of effector T cells needs to be MHC-restricted.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Zinkernagel, R. M. et al. J. exp. Med. 147, 882–896 (1978).
Dembic, Z. et al. Nature 320, 232–238 (1986).
Saito, T., Weiss, A., Miller, J., Nacross, M. A. & Germain, R. N. Nature 325, 125–130 (1987).
Doyle, C. & Strominger, J. Nature 330, 259–261 (1987).
Janeway, C. A. Jr et al. Immunol. Rev. 101, 36–67 (1988).
Gay, D. et al. Nature 328, 626–629 (1987).
Eichmann, K., Jonsson, J. I., Falk, I. & Emmrich, F. Eur. J. Immun. 17, 643–652 (1987).
Owens, T., Fazekas de St. Groth, B. & Miller, J. F. A. P. Proc. natn. Acad. Sci. U.S.A. 84, 9209–9213 (1987).
Bank, L. & Chess, L. J. exp. Med. 162, 1294–1310 (1985).
Tite, J. P., Sloan, A. & Janeway, C. A. Jr J. molec. Cell Immun. 2, 179–185 (1986).
Kubo, R. T. et al. J. Immun. 142, 2736–2742 (1989).
Pierres, A. et al. J. Immun. 132, 2775–2783 (1984).
Wilde, D., Marrack, P., Kappler, J., Dialynas, D. & Fitch, F. J. Immun. 131, 2178–2184 (1983).
Leo, O., Foo, M., Sachs, D. M., Samelson, L. M. & Bluestone, J. A. Proc. natn. Acad. Sci. U.S.A. 84, 1374–1377 (1987).
Finkel, T. H., Cambier, J. C., Kubo, R. T., Born, W., Marrack, P. & Kappler, J. W. Cell 58, 1047–1054 (1989).
Finkel, T. H., Marrack, P., Kappler, J. W., Kubo, R. T. & Cambier, J. C. J. Immun. 142, 3006–3012 (1989).
Saizawa, K., Rojo, J. & Janeway, C. A. Nature 328, 260–263 (1987).
Rivas, A., Takada, J., Koide, J., Sonderstrup-McDevitt, G. & Engleman, E. J. Immun. 140, 2912–2918 (1988).
Sellins, K. S. & Cohen, J. J. J. Immun. 139, 3199–3206 (1987).
Smith, C. A., Willimas, R., Kingston, E. J., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181–183 (1989).
Shi, Y., Sahai, B. M. & Greene, D. R. Nature 339, 625–628 (1989).
Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. T. Nature 337, 181–184 (1989).
Ucker, D. S., Ashwell, J. D. & Nickas, G. J. Immun. 143, 3461–3468 (1989).
Burton, K. Biochem. J. 62, 315–322 (1956).
Veillette, A., Bookman, M. A., Horak, E. M., Samelson, L. E. & Bolen, J. B. Nature 338, 257–259 (1989).
Qin, S., Cobbold, S., Benjamin, R. & Waldmann, H. J. expl. Med. 169, 779–794 (1989).
Weyand, C. M., Goronzy, J., Swarztrauber, K. & Fathman, C. G. Transplantation 47, 1039–1042 (1989).
Rosoff, P. M., Burakoff, S. J. & Greenstein, J. L. Cell 49, 845–862 (1987).
Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–304 (1988).
Baniyanh, M. et al. J. biol. Chem. 263, 9874–9878 (1988).
Mercep, M., Weissman, A. M., Frank, S. J., Klausner, R. D. & Ashwell, J. D. Science 246, 1162–1165 (1989).
Springer, T. A. in Monoclonal Antibodies, 185–192 (Plenum, New York, 1980).
Altevogt, P. M., Michaelis, M. & Apt, D. International Congress of Immunology, Berlin, FRG Abstr. 11-2, 43 (1989).
Trowbridge, I. S. & Omary, M. B. J. exp. Med. 154, 1517–1524 (1981).
Sarmiento, M., Glasebrook, A. L. & Fitch, F. W. J. Immun. 125, 2665–2672 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Newell, M., Haughn, L., Maroun, C. et al. Death of mature T cells by separate ligation of CD4 and the T-cell receptor for antigen. Nature 347, 286–289 (1990). https://doi.org/10.1038/347286a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/347286a0
This article is cited by
-
The co-receptor signaling model of HIV-1 pathogenesis in peripheral CD4 T cells
Retrovirology (2009)
-
The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells
Apoptosis (2007)
-
The complementary roles of deletion and regulation in transplantation tolerance
Nature Reviews Immunology (2003)
-
The associated regulators and signal pathway in rIL-16/CD4 mediated growth regulation in Jurkat cells
Cell Research (2002)
-
Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells
British Journal of Cancer (1999)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
