THE ONSET OF FAS EXPRESSION PARALLELS THE ACQUISITION OF CD8 AND CD4 IN FETAL AND ADULT ALPHA-BETA THYMOCYTES

Fas is an apoptosis-related cell surface molecule whose defective tran scription results in the lpr defect and autoimmunity. Recent analysis of Fas mRNA and protein expression in normal mice showed high expressi on in the thymus, on activated T cells, and on 5-10% of peripheral T c ells. To investigate the role of Fas in the thymus, we analyzed its ex pression in fetal and adult thymocyte subsets. Fas was not expressed o n fetal nor adult CD8(-)CD4(-) (double-negative, DN) T cell precursors . The earliest precursors that expressed low levels of FAS were the im mediate precursors of DP thymocytes that bear the CD44(-)CD25(-) CD8(I o)CD4(Io)TCR(Io) phenotype. Other DN cells that expressed Fas appeared to be either non-T cells or mature alpha beta(+) DN thymocytes. The o nset of Fas expression followed the onset of expression of CD8 and CD4 and Fas expression reached its peak in CD8(+)CD4(+) double-positive ( DP) thymocytes. Both single-positive (SP) subsets were largely Fas(+) (CD8 SP < CD4 SP) but expressed lower levels of Fas than DP cells. How ever, a majority (>60%) of the most mature HSA(Io) SP cells (2 - 5% of all SP thymocytes) were Fas- and the remainder of the HSA(Io) SP cell s was Fas(Io). We observed two main differences between Fas expression on fetal versus adult thymocytes. First, up to 90% of fetal gamma del ta(+) DN cells expressed high levels of Fas, in contrast to the very l ow expression (<7% Fas(+) cells) among adult gamma delta(+) thymocytes . Second, whereas virtually all adult DP cells were Fas(+), up to 75% of fetal day 16 DP cells were Fas(-). A possible role of Fas in T cell development is discussed in light of these results.