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Science 23 October 1992:
Vol. 258. no. 5082, pp. 653 - 656
DOI: 10.1126/science.1357752
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Articles

Science, Vol 258, Issue 5082, 653-656
Copyright © 1992 by American Association for the Advancement of Science

articles

Negative selection of precursor thymocytes before their differentiation into CD4+CD8+ cells

Y Takahama, EW Shores, and A Singer

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation.


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