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

DOUBLE-NEGATIVE THYMOCYTE SUBSETS IN CD3-ZETA CHAIN-DEFICIENT MICE - ABSENCE OF HSA(+)CD44(-)CD25(-) CELLS
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DOI:
10.1002/eji.1830240828
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发表时间:
1994-08-01
影响因子:
5.4
通讯作者:
MALISSEN, B
MALISSEN, B
中科院分区:
医学3区
文献类型:
--
作者:
CROMPTON, T;MOORE, M;MALISSEN, B

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在CD3 zeta链(zeta-/-)缺失的小鼠中检测双阴性(DN)胸腺细胞亚群。发现HSA(+)CD44(-)CD25(-)亚群缺失,DN胸腺细胞似乎直接从HSA(+)CD25(+)CD44(-)细胞分化为双阳性(DP)细胞。当检查胎儿胸腺个体发育时,我们发现从胚胎第17.5天开始,zeta-/-胚胎和杂合胎仔在CD25、CD4和CD8表达以及胸腺大小方面存在显著差异。zeta-/-胸腺细胞不能下调CD25并呈指数增长。成年胸腺细胞亚群的细胞周期状态表明,虽然HSA(+)CD25(-)CD44(-)亚群缺失,但CD25(+) DN群体中含有正常数量的循环细胞,CD25(+) DP细胞(在正常小鼠中未检测到)在G2/M + s中含有5-10%的细胞。综上所述,这些数据表明CD3 zeta链可能在T细胞发育过程中控制DN胸腺细胞的增殖中具有特定作用。我们的数据清楚地表明,人们可以将CD25(+) DN细胞分化的信号(在缺乏CD3 zeta的情况下发生)与增殖信号和细胞表面CD25的丢失分离开来。
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.