CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice
CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice
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DOI：
10.1073/pnas.101123098
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发表时间：
2001-05-22
影响因子：
11.1
通讯作者：
Chess, L
中科院分区：
文献类型：
--
作者：
Jiang, H;Braunstein, NS;Chess, L
T细胞抗原受体和MHC/肽复合物之间的三分子相互作用，以及共刺激分子和细胞因子，控制初始T细胞的活化，并决定是否辅助前体细胞分化成T辅助（TH）1或TH 2效应细胞。我们现在提出的证据表明，调节性CD 8（+）T细胞在免疫应答的进一步进化过程中提供了另一个水平的TH表型控制。这些调节性CD 8（+）T细胞在T细胞接种期间由抗原触发的CD 4（+）TH 1细胞诱导，并且在体外以T细胞抗原受体VP特异性和Qa-1限制性方式区分成熟的TH 1和TH 2细胞。在体内，对由T细胞接种诱导的实验性自身免疫性脑脊髓炎（EAE）的保护依赖于CD 8（+）T细胞，并且髓磷脂碱性蛋白反应性TH 1 V β 8（+）克隆，而不是TH 2 V β 8（+）克隆，用作疫苗T细胞，保护动物免于随后诱导的EAE。此外，在EAE第一次发作期间体内CD 8（+）T细胞的耗竭导致TH表型在继发性髓鞘碱性蛋白刺激后向TH 1倾斜。这些数据提供的证据表明，CD 8（+）T细胞控制自身免疫反应，部分是通过调节自身反应性CD 4（+）T细胞的TH表型。
Trimolecular interactions between the T cell antigen receptor and MHC/peptide complexes, together with costimulatory molecules and cytokines, control the initial activation of naive T cells and determine whether the helper precursor cell differentiates into either T helper (TH)1 or TH2 effector cells. We now present evidence that regulatory CD8(+) T cells provide another level of control of TH phenotype during further evolution of immune responses. These regulatory CD8(+) T cells are induced by antigen-triggered CD4(+) TH1 cells during T cell vaccination and, in vitro, distinguish mature TH1 from TH2 cells in a T cell antigen receptor VP-specific and Qa-1-restricted manner. In vivo, protection from experimental autoimmune encephalomyelitis (EAE) induced by T cell vaccination depends on CD8(+) T cells, and myelin basic protein-reactive TH1 V beta8(+) clones, but not TH2 V beta8(+) clones, used as vaccine T cells, protect animals from subsequent induction of EAE. Moreover, in vivo depletion of CD8(+) T cells during the first episode of EAE results in skewing of the TH phenotype toward TH1 upon secondary myelin basic protein stimulation. These data provide evidence that CD8(+) T cells control autoimmune responses, in part, by regulating the TH phenotype of self-reactive CD4(+) T cells.