Sheard Michael A, Liu Cunlan, Takahama Yousuke
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
Eur J Immunol. 2004 Jan;34(1):25-35. doi: 10.1002/eji.200324460.
In normal mice, more than 10% of thymocytes in the CD4+CD8- and CD4-CD8+ single-positive (SP) subsets express a medium level of CD3 on the cell surface. However, the fate of CD3medium cells is unclear. The CD3medium SP subpopulations might contain (i) cells in an immature stage of the pathways leading to CD3high cells, (ii) cells in developmental pathways that do not lead to CD3high cells, or (iii) cells that have been negatively selected. We found that sorted CD3medium CD4+CD8- thymocytes from adult mice up-regulated CD3 to high levels in reaggregation thymus organ culture. Unlike their CD3high counterparts, CD3medium CD4+CD8- thymocytes were unable to undergo chemotaxis towards the chemokines CCL19 and CCL21. CD3medium thymocytes of both CD4+CD8- and CD4-CD8+ subsets were also considerably more responsive than CD3high SP cells to apoptotic signals induced in vitro by ligation of CD95 (Fas/APO-1) or by dexamethasone. In both SP subsets, a higher frequency of thymocytes expressing forbidden Vbeta+ T cell receptors reactive with endogenous mammary tumor virus superantigens was found in CD3medium subpopulations than in CD3high subpopulations. These findings argue that the CD3medium SP thymocyte subpopulations contain apoptosis-susceptible precursor cells of CD3high SP cells and are subject to negatively selecting pressures.
在正常小鼠中，CD4⁺CD8⁻和CD4⁻CD8⁺单阳性（SP）亚群中超过10%的胸腺细胞在细胞表面表达中等水平的CD3。然而，CD3中等水平细胞的命运尚不清楚。CD3中等水平的SP亚群可能包含：（i）处于通向CD3高水平细胞途径的未成熟阶段的细胞；（ii）处于不导致CD3高水平细胞的发育途径中的细胞；或（iii）已被阴性选择的细胞。我们发现，从成年小鼠中分离出的CD3中等水平的CD4⁺CD8⁻胸腺细胞在重组胸腺器官培养中CD3上调至高水平。与CD3高水平的对应细胞不同，CD3中等水平的CD4⁺CD8⁻胸腺细胞无法对趋化因子CCL19和CCL21进行趋化运动。CD4⁺CD8⁻和CD4⁻CD8⁺亚群的CD3中等水平胸腺细胞对CD95（Fas/APO - 1）连接或地塞米松在体外诱导的凋亡信号的反应也比CD3高水平的SP细胞强烈得多。在两个SP亚群中，与内源性乳腺肿瘤病毒超抗原反应的表达禁忌Vβ⁺T细胞受体的胸腺细胞在CD3中等水平亚群中的频率高于CD3高水平亚群。这些发现表明，CD3中等水平的SP胸腺细胞亚群包含对凋亡敏感的CD3高水平SP细胞前体细胞，并受到阴性选择压力。
