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.