DOUBLE-NEGATIVE THYMOCYTE SUBSETS IN CD3-ZETA CHAIN-DEFICIENT MICE - ABSENCE OF HSA(-)CD25(-) CELLS()CD44()

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 directl y from HSA(+)CD25(+)CD44(-) cells to double-positive (DP) cells. When fetal thymic ontogeny was examined,we found a marked difference betwee n 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 alth ough the HSA(+)CD25(-)CD44(-) subset was missing, the CD25(+) DN popul ation contained normal numbers of cycling cells, and the CD25(+) DP ce lls (which were not detectable in normal mice) contained 5-10% cells i n 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 thymo cytes during T cell development. Our data clearly show that one can di ssociate the signal for a CD25(+) DN cell to differentiate (which occu rs in the absence of CD3 zeta), from a signal to proliferate and from loss of cell surface CD25.