Abstract
MATURE T cells express either CD4 or CD8 on their surface. Most helper T cells express CD4, which binds to class II major histocompatibility complex (MHC) proteins, and most cytotoxic T cells express CD8, which binds to class I MHC proteins. In the thymus, mature CD4+CD8− and CD4− CD8+ T cells expressing αβ T-cell antigen receptors (TCR) develop from immature thymocytes through CD4+CD8+αβTCR+ intermediates1. Experiments using mice transgenic forαβTCR2–5 suggest that the specificity of the TCR determines the CD4/CD8 phenotype of mature T cells. These results, however, do not indicate how a T cell differentiates into the CD4 or CD8 lineage. Here we show that the CD4 transmembrane region and/or cytoplasmic tail mediates the delivery of a specific signal that directs differentiation of T cells to a CD4 lineage. We generated transgenic mice expressing a hybrid molecule composed of the CD8α extracellular domains linked to the CD4 transmembrane region and cytoplasmic tail. We predicted that this hybrid molecule would bind to class I MHC proteins through the extracellular domains but deliver the intracellular signals characteristic of CD4. By crossing our transgenic mice with mice expressing a transgenic αβTCR specific for a particular antigen plus class I MHC protein, we were able to express the hybrid molecule in developing thymocytes expressing the class I MHC-restricted TCR. Our results show that the signal transduced by the hybrid molecule results in the differentiation of immature thymocytes expressing a class I-restricted TCR into mature T cells expressing CD4.
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
Fowlkes, B. J. & Pardoll, D. M. Adv. Immun. 44, 207–264 (1989).
Teh, H.-S. et al. Nature 335, 229–233 (1988).
Sha, W. C. et al. Nature 335, 271–274 (1988).
Berg, L. J. et al. Cell 58, 1035–1046 (1989).
Kaye, J. et al. Nature 341, 746–749 (1989).
Kisielow, P., Blüthman, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–746 (1988).
Veillete, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–308 (1988).
Veillete, A., Zúñiga-Pflücker, J. C., Bolen, J. B. & Kruisbeek, A. M. J. exp. Med. 170, 1671–1680 (1989).
Luo, K. & Sefton, B. M. Molec. cell. Biol. 10, 5305–5313 (1990).
Robey, E. A. et al. Cell 64, 99–107 (1991).
Borgulya, P., Kishi, H., Müller, U., Kirberg, J. & von Boehmer, H. EMBO J. 10, 913–918 (1991).
Zamoyska, R. et al. Nature 342, 278–281 (1981).
Gunning, P., Leavitt, J., Muscat, G., Ng, S. & Kedes, L. Proc. natn. Acad. Sci. U.S.A. 84, 4831–4835 (1987).
Gorman, S. D., Tourvieille, B. & Parnes, J. R. Proc. natn. Acad. Sci. U.S.A. 84, 7644–7648 (1987).
Sarmiento, M. et al. Immunol. Rev. 68, 135–169 (1982).
Teh, H.-S., Kishi, H., Scott, B. & von Boehmer, H. J. exp. Med. 169, 795–806 (1989).
Kisielow, P., Teh, S.-H., Blüthman, H. & von Boehmer, H. Nature 335, 730–733 (1988).
Teh, H.-S. et al. Nature 335, 229–233 (1988).
Bevan, M. J. Nature 269, 417–418 (1977).
Zinkernagel, R. H. et al. J. exp. Med. 147, 882–896 (1978).
von Boehmer, H., Haas, W. & Jerne, N. K. Proc. natn. Acad. Sci. U.S.A. 75, 2434–2442 (1978).
Kappler, J. & Marrack, P. J. J. exp. Med. 148, 1510–1522 (1978).
Ledbetter, J. A., Seaman, W., Tsu, T. & Herzenberg, L. A. J. exp. Med. 153, 1503–1516 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Seong, R., Chamberlain, J. & Parnes, J. Signal for T-cell differentiation to a CD4 cell lineage is delivered by CD4 transmembrane region and/or cytoplasmic tail. Nature 356, 718–720 (1992). https://doi.org/10.1038/356718a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/356718a0
This article is cited by
-
Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice
Nature Reviews Immunology (2008)
-
Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation
Oncogene (2004)
-
CD4/CD8-lineage differentiation in the thymus: from nuclear effectors to membrane signals
Nature Reviews Immunology (2004)
-
The influence of the thymic environment on the CD4-versus-CD8 T lineage decision
Nature Immunology (2003)
-
T-cell development and the CD4–CD8 lineage decision
Nature Reviews Immunology (2002)
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.