Volkmann A, Barthlott T, Weiss S, Frank R, Stockinger B
Division of Molecular Immunology, The National Institute for Medical Research, London, United Kingdom.
J Exp Med. 1998 Sep 21;188(6):1083-9. doi: 10.1084/jem.188.6.1083.
CD4/CD8 lineage decision is an important event during T cell maturation in the thymus. CD8 T cell differentiation usually requires corecognition of major histocompatibility complex (MHC) class I by the T cell receptor (TCR) and CD8, whereas CD4 T cells differentiate as a consequence of MHC class II recognition by the TCR and CD4. The involvement of specific peptides in the selection of T cells expressing a particular TCR could be demonstrated so far for the CD8 lineage only. We used mice transgenic for an MHC class II-restricted TCR to investigate the role of antagonistic peptides in CD4 T cell differentiation. Interestingly, antagonists blocked the development of CD4(+) cells that normally differentiate in thymus organ culture from those mice, and they induced the generation of CD8(+) cells in thymus organ culture from mice impaired in CD4(+) cell development (invariant chain-deficient mice). These results are in line with recent observations that antagonistic signals direct differentiation into the CD8 lineage, regardless of MHC specificity.
CD4/CD8谱系决定是胸腺中T细胞成熟过程中的一个重要事件。CD8 T细胞分化通常需要T细胞受体（TCR）和CD8对主要组织相容性复合体（MHC）I类分子的共同识别，而CD4 T细胞则是由于TCR和CD4对MHC II类分子的识别而分化。到目前为止，仅在CD8谱系中证实了特定肽在选择表达特定TCR的T细胞中的作用。我们使用了针对MHC II类限制性TCR的转基因小鼠来研究拮抗肽在CD4 T细胞分化中的作用。有趣的是，拮抗剂阻断了在胸腺器官培养中正常分化的CD4(+)细胞的发育，这些细胞来自那些小鼠，并且它们在胸腺器官培养中诱导了CD4(+)细胞发育受损的小鼠（恒定链缺陷小鼠）产生CD8(+)细胞。这些结果与最近的观察结果一致，即拮抗信号引导分化为CD8谱系，而与MHC特异性无关。
