DEVELOPMENT OF MATURE CD8+ THYMOCYTES - SELECTION RATHER THAN INSTRUCTION
DEVELOPMENT OF MATURE CD8+ THYMOCYTES - SELECTION RATHER THAN INSTRUCTION
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DOI：
10.1126/science.8102208
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发表时间：
1993-08-13
期刊：
影响因子：
56.9
通讯作者：
GERMAIN, RN
中科院分区：
文献类型：
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作者：
VANMEERWIJK, JPM;GERMAIN, RN
通过比较野生型小鼠和β 2-微球蛋白（β 2 M）突变型小鼠（MHCI类表达缺陷）和成熟CD 8+细胞中胸腺细胞亚群，研究了主要组织相容性复合体（MHC）分子在T细胞分化中的作用。基于表面标志物、糖皮质激素抗性、体外分化能力和β 2 M-/-小鼠中的缺失，具有α T细胞受体（TCR α）高表达的CD 4（中间）CD 8hi细胞被鉴定为已被MHC I类阳性选择以发育成成熟CD 8 + T细胞。野生型和β 2 M-/-动物中均存在活化的CD 4（int）CD 8hi细胞，其携带中等量而非高量的TCR。这些数据表明，MHC I类分子的识别是完全成熟为CD 8 + T细胞所必需的，但不是受体启动的CD 8+谱系的承诺，与胸腺细胞发育的随机（选择）模型一致。
The role of major histocompatibility complex (MHC) molecules in T cell differentiation was investigated by comparison of thymocyte subpopulations in wild-type mice and beta2-microglobulin (beta2M) mutant mice deficient in MHC class I expression and mature CD8+ cells. On the basis of surface markers, glucocorticoid resistance, in vitro differentiation capacity, and absence in beta2M-/- mice, CD4(intermediate)CD8hi cells with high expression of alphabeta T cell receptor (TCRalphabeta) were identified as having been positively selected by MHC class I for development into mature CD8+ T cells. Activated CD4(int)CD8hi cells bearing intermediate rather than high amounts of TCR were present in both wild-type and beta2M-/- animals. These data suggest that recognition of MHC class I molecules is required for full maturation to CD8+ T cells, but not for receptor-initiated commitment to the CD8+ lineage, consistent with a stochastic (selection) model of thymocyte development.