CD7-negative T cells represent a separate differentiation pathway in a subset of post-thymic helper T cells

The absence of CD7 protein and the corresponding mRNA is a stable feature in a subset of normal circulating CD4+ memory T cells. It is still unresolved whether the CD7- subset represents a specific T-cell lineage. 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 non-expression of the CD7 antigen. Comparing different T-cell activation pathways (TCR/CD3, CD2), we observed that alternative signals were critically involved in the development of CD4+ CD7- T cells. Peak mean numbers of CD7- memory cells occurred after 3-5 cycles of restimulation in vitro. Naive T cells that had undergone repeated stimulations 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 re-express the antigen during further propagation of separated T-cell subsets. In CD7- cells no CD7 mRNA was monitored, indicating transcriptional regulation of CD7 expression. Certain differentiation-related antigens, including the cutaneous lymphocyte antigen CLA, were preferentially expressed on CD7- T cells. We suggest that absence of CD7 expression in a subset of CD4+ memory cells reflects a separate and stable differentiation state occurring late in the immune response. These T cells may represent the physiological counterpart of malignant T cells in certain forms of cutaneous T-cell lymphoma.