Functional commitment to helper T cell lineage precedes positive selection and is independent of T cell receptor MHC specificity
Abstract
Thymocyte differentiation proceeds from double positive CD4⁺CD8⁺ to single positive T cells. It has been proposed that this process occurs by an instructive or a stochastic mechanism. In this report, we show that in recombination-deficient mice (RAG-1^(-/-)) constitutive expression of a CD8 transgene allows maturation of CD4⁺ (CD8tg⁺) cells, which express mature levels of a transgenic class I-restricted T cell receptor, F5. Rescued F5⁺CD4⁺ (CD8tg⁺) cells have equivalent levels of T cell receptor expression as CD8end⁺ cells, respond to cognate antigen and, upon stimulation, they exhibit a phenotype characteristic of CD4⁺ helper T cells. These data are consistent with a model of differentiation that predicts that thymocytes become functionally committed to a helper or cytotoxic lineage before the final step of positive selection and independently of MHC specificity of their T cell receptor.
Additional Information
© 1994 by Cell Press. Received 28 February 1994, Revised 1 June 1994. The authors wish to thank Mrs. M. Burke for expert secretarial assistance, Ms. T. Norton for excellent animal husbandry, and Mr. J. Brock for graphics work. Ors. A. Mellor, B. Stockinger, R. Zamoyska, and G. Klaus (National Institute for Medical Research, London) for scientific discussions and reagents. Ors. D. Gray (Royal Postgraduate Medical School, Hammersmith, London) and R. Noelle (Dartmouth Medical School, New Hampshire) for MAbs. P. C. and D. M. were supported by grants from the European Community.Additional details
- Eprint ID
- 103166
- Resolver ID
- CaltechAUTHORS:20200513-080630337
- European Community
- Created
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2020-05-13Created from EPrint's datestamp field
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2021-11-16Created from EPrint's last_modified field