A role for c-myc in the regulation of thymocyte differentiation and possibly positive selection.
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.
Broussard-Diehl
C
C
Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
Bauer
S R
SR
Scheuermann
R H
RH
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D016259:Genes, myc / Q000276:immunology*; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*