Double‐negative thymocyte subsets in CD3′ chain‐deficient mice: Absence of HSA+CD44−CD25− cells

Abstract

Double-negative (DN) thymocyte subsets were examined in mice deficient in the CD3′ chain (ζ −/−). 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 ζ −/− embryos and heterozygous littermates from embryonic day 17.5, in terms of CD25, CD4 and CD8 expression, and thymus size. The ζ −/− 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′ 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′), from a signal to proliferate and from loss of cell surface CD25.