Intrathymic Differentiation of V ' y 3 T Cells

Whereas there is considerable information on the phenotypic and functional maturation of T cell receptor (TCR) ot/3 thymocytes, comparatively little is known of the maturational processes that affect development of TCR-3//8 thymocytes. One class of 3,/8 T cells, those bearing the V3'3 gene product, are generated only during the early fetal stages of thymic development, and then migrate to the skin. Here we examine the intrathymic differentiation of these V'y3 + cells. The earliest V'y3 cells to appear in the thymus expressed low levels of TCR (V3~3 l~ and high levels of heat stable antigen (HSA). Over the next few days, V3'3 + thymocytes appeared which expressed high levels of TCR (V3/3hig h) and very low levels of HSA. The antigens CD5, CD45RB, and MEL14 were also differentially expressed on V'y3 l~ versus V3~3high thymocytes, but the shift in expression was the opposite as compared with immature and mature TCK-odB thymocytes. Transfer experiments of sorted V3,31~ h thymocytes to SCID thymic lobes showed that these cells were indeed the precursors of V3~3high/HSA l~ thymocytes. The phenotype of the V3/3 high thymocytes was similar to that of the postthymic V'y3 + cells found in the skin of adult mice. The differentiation of Vy3 l~ in V3,3hig h thymocytes was also observed in fetal thymic organ culture. Addition of cyclosporin A (CsA) to these cultures had little effect on the appearance of V3,31~ h cells, but blocked the appearance of V'y3high/HSA l~ cells. These results show that, like c~/3 T cells, V3,3 + thymocytes differentiate from TCR l~ precursors to cells with a mature phenotype and that CsA inhibits this transition.