Goldrath A W, Hogquist K A, Bevan M J
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Immunity. 1997 May;6(5):633-42. doi: 10.1016/s1074-7613(00)80351-9.
The absence of cytotoxic T lymphocyte activity and the failure of MHC class I-restricted T cell receptor (TCR) transgenic thymocytes to mature in CD8alpha-deficient mice suggest that CD8 may be essential for CD8 lineage commitment. We report that variants of the antigenic peptide that delete TCR transgenic thymocytes from CD8 wild-type but not CD8alpha-deficient mice can restore positive selection of CD8 lineage cells in the absence of CD8. The positively selected cells down-regulate CD4, up-regulate TCR, respond to the antigenic peptide, and express CD8beta mRNA. Interestingly, there was no enhanced selection of CD4+ T cells, implying that the TCR-MHC interaction, even in the absence of CD8, provided instructive signaling for commitment to the CD8 lineage. Our results are discussed in terms of recent models of T cell lineage commitment.
细胞毒性T淋巴细胞活性的缺失以及MHC I类限制性T细胞受体（TCR）转基因胸腺细胞在CD8α缺陷小鼠中未能成熟，这表明CD8可能对CD8谱系的定向分化至关重要。我们报道，从CD8野生型而非CD8α缺陷小鼠中删除TCR转基因胸腺细胞的抗原肽变体，可在无CD8的情况下恢复CD8谱系细胞的阳性选择。阳性选择的细胞下调CD4，上调TCR，对抗原肽作出反应，并表达CD8β mRNA。有趣的是，CD4+ T细胞没有增强的选择，这意味着即使在没有CD8的情况下，TCR-MHC相互作用也为定向分化为CD8谱系提供了指导性信号。我们根据最近的T细胞谱系定向分化模型对结果进行了讨论。
