Double-negative thymocyte subsets in CD3 zeta chain-deficient mice: absence of HSA+CD44-CD25- cells.

Double-negative (DN) thymocyte subsets were examined in mice deficient in the CD3 zeta chain (zeta-/-). The HSA+CD44-CD25- subset was found to be missing, and DN thymocytes seemed to differentiate directly from HSA+CD25+CD44- cells to double-positive (DP) cells. When fetal thymic ontogeny was examined, we found a marked difference between zeta-/- embryos and heterozygous littermates from embryonic day 17.5, in terms of CD25, CD4 and CD8 expression, and thymus size. The zeta-/- thymocytes failed to down-regulate CD25 and to expand exponentially. The cell cycle status of adult thymocyte subsets indicated that although the HSA+CD25-CD44- subset was missing, the CD25+ DN population contained normal numbers of cycling cells, and the CD25+ DP cells (which were not detectable in normal mice) contained 5-10% cells in G2/M+S. Taken together these data suggest that the CD3 zeta chain might have a specific role in the control of proliferation of DN thymocytes during T cell development. Our data clearly show that one can dissociate the signal for a CD25+ DN cell to differentiate (which occurs in the absence of CD3 zeta), from a signal to proliferate and from loss of cell surface CD25.