Broussard-Diehl C, Bauer S R, Scheuermann R H
Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
J Immunol. 1996 May 1;156(9):3141-50.
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.
胸腺细胞分化的目的是建立T细胞库并清除无功能的和自身反应性T细胞。在对这一过程的潜在调节因子进行分析时，我们发现c-myc的表达在胸腺细胞早期分化过程中显著下调，随后在CD4+8+细胞中随着TCR/CD3一起上调。在胸腺细胞中组成性表达c-myc的转基因Eβ-myc小鼠比对照小鼠有更大比例的胸腺细胞具有高TCR/CD3和低热稳定抗原-1表达，并且具有CD4+CD8low表型的过渡细胞数量增加。通过增殖和激活标志物CD69的诱导来衡量，成熟的Eβ-myc T细胞通过其TCR/CD3复合物对激活的反应不如对照细胞强烈。这些结果与一种假说一致，即通过TCR/CD3激活未成熟T细胞会诱导c-myc上调，并驱动胸腺细胞通过阳性选择的初始阶段。
