Lck Activity Controls CD4/CD8 T Cell Lineage Commitment
Abstract
Thymocytes carrying MHC class I–restricted TCRs differentiate into CD8 T cells, while those recognizing MHC class II become CD4 T cells. The mechanisms underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinase Lck binds with more affinity to CD4 than CD8, it has been proposed as a candidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class II–restricted TCR develop into functional CD8 T cells when Lck activity is reduced. Conversely, thymocytes carrying a class I–restricted TCR develop into functional CD4 T cells when Lck activity is increased. These results directly show that quantitative differences in the Lck signal control the CD4/CD8 lineage decision.
Additional Information
© 2000 Cell Press. Received 16 November 1999, Revised 17 January 2000. We thank R. M. Perlmutter for providing the dLGF and dLGKR mice; R. Diamond for the cell sorts; H. Wang for the PCR primers; D. Miller, L. Anonuevo, and B. Kennedy for animal husbandry; and S. Kovats, P. W. Sternberg, P. J. Bjorkman, and A. Y. Rudensky for suggestions and helpful discussions. G. H-H. was supported by funding from the Stowers Institute for Medical Research. J. A-I. is a Pew Scholar. This work was supported by the Pew Scholar Program in the biomedical sciences and by National Institutes of Health grant number AI45072-01A1 to J. A-I.Additional details
- Eprint ID
- 74194
- DOI
- 10.1016/S1074-7613(00)80184-3
- Resolver ID
- CaltechAUTHORS:20170209-113011357
- Stowers Institute for Medical Research
- Pew Charitable Trust
- AI45072-01A1
- NIH
- Created
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2017-02-09Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field