DeKoning J, Carbone F R, Kaye J
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Int Immunol. 1995 Apr;7(4):541-9. doi: 10.1093/intimm/7.4.541.
Experiments in transgenic mice have demonstrated that thymocyte differentiation into the mature CD4+ helper or CD8+ cytotoxic T cell lineage is ultimately dependent upon the specificity of the TCR for class II or class I MHC molecules respectively. However, the initial mechanistic events involved in this process remain unclear. To address this issue, we have expressed a TCR specific for an ovalbumin peptide and the Kb class I MHC molecule in the DPK CD4+CD8+ precursor T cell line. This cell line originally expressed a TCR specific for a pigeon cytochrome c peptide and class II MHC molecules and has been shown previously to differentiate into CD4+CD8- cells upon recognition of antigen in vitro or thymic epithelial cells in vivo. Surprisingly, we find that recognition of either class I or class II MHC by these cells initiates differentiation into the CD4+ lineage and induces down-regulation of recombination associated genes. Unlike recognition of class II MHC, however, recognition of class I MHC does not induce full maturation. These results support a model in which (i) commitment to the CD4 lineage occurs prior to positive selection and (ii) CD4 lineage commitment is associated with a requirement for activation by a class II MHC-specific TCR in order to complete differentiation.
转基因小鼠实验表明，胸腺细胞分别分化为成熟的CD4⁺辅助性T细胞或CD8⁺细胞毒性T细胞谱系最终取决于TCR对II类或I类MHC分子的特异性。然而，这一过程中涉及的初始机制事件仍不清楚。为了解决这个问题，我们在DPK CD4⁺CD8⁺前体T细胞系中表达了一种针对卵清蛋白肽和Kb I类MHC分子的TCR。该细胞系最初表达一种针对鸽细胞色素c肽和II类MHC分子的TCR，并且先前已证明在体外识别抗原或体内识别胸腺上皮细胞后可分化为CD4⁺CD8⁻细胞。令人惊讶的是，我们发现这些细胞识别I类或II类MHC都会启动向CD4⁺谱系的分化，并诱导重组相关基因的下调。然而，与识别II类MHC不同，识别I类MHC不会诱导完全成熟。这些结果支持了一个模型，即（i）在阳性选择之前就确定了向CD4谱系的分化，并且（ii）CD4谱系的确定与需要由II类MHC特异性TCR激活以完成分化有关。
