Lucas B, Marodon G, Penit C
INSERM Unit 345, Necker Institute, Paris, France.
J Immunol. 1996 Mar 1;156(5):1743-47.
Thymocytes with a low expression of CD4 and an intermediate density of the TCR (CD4low TCRint) were analyzed for phenotype, MHC dependence, production kinetics, and TCR repertoire to investigate their position in the intrathymic T cell maturation process. Comparison of normal and MHC-deficient mice showed that the CD4low TCRint cell subset was MHC class II dependent, as this subpopulation could not be defined in MHC class II- or double (class I and II)-deficient mice. These thymocytes were heat-stable Aghigh and CD69+, thus immature and recently engaged in a TCR interaction, probably with MHC class II molecules. Their generation kinetics were studied in two systems: development of exogenous bone marrow cells transferred into RAG-2-/- mice, and pulse labeling with bromodeoxyuridine. In both systems, CD4low TCRint cells were produced well before CD4low TCRhigh cells, the direct precursors of CD8 single-positive cells. Their production paralleled that of CD4high TCRint cells, but they were different than these thymocytes in their smaller cell size. Moreover, they had the same V beta 6 frequency in Mls-1a and Mls-1b mice, suggesting that these cells could be undergoing a negative selection process. The data here clearly demonstrate that CD4low TCRint thymocytes do not belong to the CD8 lineage maturation pathway, and suggest that these cells could represent a MHC class II-restricted dead-end subset.
对CD4表达低且TCR密度中等（CD4low TCRint）的胸腺细胞进行表型、MHC依赖性、产生动力学和TCR库分析，以研究它们在胸腺内T细胞成熟过程中的位置。正常小鼠和MHC缺陷小鼠的比较表明，CD4low TCRint细胞亚群依赖于MHC II类分子，因为在MHC II类缺陷或双缺陷（I类和II类）小鼠中无法定义该亚群。这些胸腺细胞热稳定Aghigh且CD69+，因此不成熟且最近参与了TCR相互作用，可能是与MHC II类分子相互作用。在两个系统中研究了它们的产生动力学：将外源性骨髓细胞转移到RAG-2-/-小鼠中的发育过程，以及用溴脱氧尿苷进行脉冲标记。在这两个系统中，CD4low TCRint细胞比CD8单阳性细胞的直接前体CD4low TCRhigh细胞产生得早得多。它们的产生与CD4high TCRint细胞平行，但在细胞大小上比这些胸腺细胞小。此外，它们在Mls-1a和Mls-1b小鼠中的Vβ6频率相同，表明这些细胞可能正在经历阴性选择过程。此处的数据清楚地表明，CD4low TCRint胸腺细胞不属于CD8谱系成熟途径，并表明这些细胞可能代表一个MHC II类限制性的终末亚群。
