The onset of Fas expression parallels the acquisition of CD8 and CD4 in fetal and adult αβ thymocytes

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Abstract
Fas is an apoptosis-related cell surface molecule whose defective transcription results in the Ipr defect and autolmmunlty. Recent analysis of Fas mRNA and protein expression in normal mice showed high expression in the thymus, on activated T cells, and on 5–10% of peripheral T cells. To investigate the role of Fas in the thymus, we analyzed its expression in fetal and adult thymocyte subsets. Fas was not expressed on fetal nor adult CD8−CD4− (double-negative, DN) T cell precursors. The earliest precursors that expressed low levels of FAS were the immediate precursors of DP thymocytes that bear the CD44−CD25−CD8toCD4toCRto phenotype. Other DN cells that expressed Fas appeared to be either non-T cells or mature αβ+ DN thymocytes. The onset 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. However, a majority (>60%) of the most mature HSAlo SP cells (2–5% of all SP thymocytes) were Fas− and the remainder of the HSAlo SP cells was Faslo. We observed two main differences between Fas expression on fetal versus adult thymocytes. First, up to 90% of fetal γδ+ DN cells expressed high levels of Fas, In contrast to the very low expression (+ cells) among adult γδ+ 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.

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