CD7-NEGATIVE T-CELLS REPRESENT A SEPARATE DIFFERENTIATION PATHWAY IN A SUBSET OF POSTTHYMIC HELPER T-CELLS

The absence of CD7 protein and the corresponding mRNA is a stable feat ure in a subset of normal circulating CD4(+) memory T cells. II is sti ll unresolved whether the CD7(-) subset represents a specific T-cell l ineage. Here we show that repeated stimulation of highly purified CD4( +) CD45RA(+)CD45RO(-) naive T cells in vitro leads to the development of a distinct memory subset that is defined by the expression versus n on-expression of the CD7 antigen. Comparing different T-cell activatio n pathways (TCR/CD3, CD2), we observed that alternative signals were c ritically involved in the development of CD4(+) CD7(-) T cells. Peak m ean numbers of CD7(-) memory cells occurred after 3-5 cycles of restim ulation in vitro. Naive T cells that had undergone repealed stimulatio ns were harvested and sorted into CD7(+) and CD7(-) subsets. The vast majority (> 97%) of CD7(+) T cells retained their expression, whereas the CD7(-) population did not reexpress the antigen during further pro pagation of separated T-cell subsets. In CD7(-) cells no CD7 mRNA was monitored, indicating transcriptional regulation of CD7 expression. Ce rtain differentiation-related antigens, including the cutaneous lympho cyte antigen CLA, were preferentially expressed on CD7(-) T cells. We suggest that absence of CD7 expression in a subset of CD4(+) memory ce lls reflects a separate and stable differentiation state occurring lat e in the immune response. These T cells may represent the physiologica l counterpart of malignant T cells in certain forms of cutaneous T-cel l lymphoma.