Wack A, Corbella P, Harker N, Roderick K, Norton T, Williams K, Williams O, Kioussis D
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
J Immunol. 1999 Aug 1;163(3):1162-9.
In this paper, we address the question whether CD4 and MHC class II expression are necessary for the development of the T helper lineage during thymocyte maturation and for activation-induced Th2 responses. To bypass the CD4-MHC class II interaction requirements for positive selection and activation, we used mice that are doubly transgenic for CD8 and for the MHC class I-restricted TCR F5. This transgene combination leads to MHC class I-dependent maturation of CD4 lineage cells. Upon activation, these CD4 lineage T cells secrete IL-4 and give help to B cells but show no cytotoxic activity. Remarkably, neither MHC class II nor CD4 expression are necessary for the generation and helper functions of these cells. This suggests that under normal conditions, coreceptor-MHC interactions are necessary to ensure the canonical combinations of coreceptor and function in developing thymocytes, but that they do not determine functional commitment. Our results also imply that expression of the CD4 gene does not influence, but is merely associated with the decision to establish the T helper program. In addition, we show that activation through TCR-MHC class I interactions can induce Th2 responses independently of CD4 and MHC class II expression.
在本文中，我们探讨了CD4和MHC II类分子的表达对于胸腺细胞成熟过程中辅助性T细胞谱系的发育以及激活诱导的Th2反应是否必要的问题。为了绕过阳性选择和激活对CD4-MHC II类分子相互作用的需求，我们使用了同时转染了CD8和MHC I类分子限制性TCR F5的双转基因小鼠。这种转基因组合导致了CD4谱系细胞依赖MHC I类分子的成熟。激活后，这些CD4谱系T细胞分泌IL-4并为B细胞提供辅助，但不表现出细胞毒性活性。值得注意的是，这些细胞的产生和辅助功能既不需要MHC II类分子的表达，也不需要CD4的表达。这表明在正常情况下，共受体与MHC的相互作用对于确保发育中的胸腺细胞中共受体和功能的典型组合是必要的，但它们并不能决定功能的定向。我们的结果还意味着CD4基因的表达并不影响，而仅仅是与建立辅助性T细胞程序的决定相关。此外，我们表明通过TCR-MHC I类分子相互作用的激活可以独立于CD4和MHC II类分子的表达诱导Th2反应。
