In vivo modulation of the distribution of thymocyte subsets: effects of estrogen on the expression of different T cell receptor V beta gene families in CD4-, CD8- thymocytes.

Estrogen treatment of mice has been shown to deplete CD4+, CD8+ double-positive (DP) thymocytes and to alter the relative proportion of CD4+ and CD8+ single-positive (SP) thymocytes. In this work, we have studied the effect of the steroid hormone 17 beta-estradiol (E2) on the different subsets of CD4-/CD8- double-negative (DN) thymocytes by analyzing the expression of CD5, CD3-epsilon and of several V beta gene family products of the T cell antigen receptor (TCR). After in vivo administration of E2 a significant decrease in the number and proportion of dull CD5+, CD3-, beta-TCR- DN thymocytes was observed. In contrast E2 treatment significantly increased the proportion of bright CD5+, CD3+, beta-TCR+ DN cells. The E2-induced increase in DN/TCR+ cells was observed for subsets expressing V beta 6, V beta 8, and V beta 11, but not V beta 3 gene products of the TCR. Thus, estrogen administration results in a selective inbalance of the DN thymocyte subsets by depleting an immature, dull CD5+, CD3-, TCR beta- DN subset, while enriching a mature, bright CD5+, CD3+, TCR beta+ DN subset of cells. In addition to TCR beta+ DN thymocytes, an increased proportion of CD4+ and CD8+ SP thymocytes expressing V beta 8, V beta 6, and V beta 11, but not V beta 3, TCR proteins was also observed after E2 administration. An involvement of intrathymic cytokine production in mediating the hormone action is suggested by the ability of estrogen to increase the levels of IL-1 alpha mRNA of intact thymus. Our data suggest that estrogen exerts its effects on a broad range of immature cells, including dull CD5+, CD3-, beta-TCR- DN and DP thymocytes.