The Journal of Immunology, Vol 156, Issue 9 3141-3150, Copyright © 1996 by American Association of Immunologists

ARTICLES

A role for c-myc in the regulation of thymocyte differentiation and possibly positive selection

C Broussard-Diehl, SR Bauer and RH Scheuermann
Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.

The purpose of thymocyte differentiation is to establish the T cell repertoire and eliminate nonfunctional and autoreactive T cells. In an analysis of potential regulators of this process, we have found that c- myc expression is down-regulated dramatically during early thymocyte differentiation and subsequently up-regulated along with TCR/CD3 in CD4+8+ cells. Transgenic E beta-myc mice that constitutively express c- myc in thymocytes have a larger proportion of thymocytes with high TCR/CD3 and low heat-stable antigen-1 expression than controls, and an increase in the number of transitional cells with a CD4+CD8low phenotype. Mature E beta-myc T cells respond less vigorously than controls to activation through their TCR/CD3 complex, as measured by proliferation and induction of the activation marker CD69. These results are consistent with a hypothesis in which activation of immature T cells through TCR/CD3 induces c-myc up-regulation and drives thymocytes through the initial stage of positive selection.

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