The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model
The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model
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DOI：
10.1093/intimm/dxh170
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Takatsu, K
中科院分区：
文献类型：
--
作者：
Tamura, T;Ariga, H;Takatsu, K
CD4(+)Th1细胞在诱导细胞介导的免疫反应中起着关键作用，而细胞免疫反应对于根除细胞内病原体是重要的。多肽-25是结核分枝杆菌Ag85B的主要Th1表位，在I-A(B)小鼠体内具有免疫原性。为了阐明TCR和干扰素-γ/IL-12信号在Th1诱导中的作用，我们建立了表达TCR-25反应性克隆T细胞的TCRα链和β链的TCR转基因小鼠(P25 TCR-TG)，并从P25 TCR-TG分析了CD4(+)T细胞的Th1发育。在抗CD3抗体的刺激下，P25 TCR-TG中的初始CD4(+)T细胞可分化为Th1和Th2细胞。在中性条件下，在I-A(B)脾抗原提呈细胞存在的情况下，P25 TCR-TG中的初始CD4(+)T细胞在多肽-25刺激下优先发展Th1细胞。相反，多肽-25的突变体只能诱导Th2分化。即使在抗干扰素-γ和抗IL-12存在的情况下，也能观察到多肽-25诱导的Th1分化。此外，来自STAT1缺陷的P25 TCR-TG的原始CD4(+)T细胞也在多肽-25刺激下分化为Th1细胞。此外，负载多肽-25的I-A(B)转基因的中国仓鼠卵巢细胞在没有干扰素-γ或IL-12的情况下，诱导P25 TCR-TG向初始的CD4(+)T细胞分化为Th1。这些结果表明，肽-25/I-A(B)和TCR之间的相互作用可能主要影响初始CD4(+)T细胞向Th1亚群分化的命运的决定。
CD4(+) Th1 cells play a critical role in the induction of cell-mediated immune responses that are important for the eradication of intracellular pathogens. Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and is immunogenic in I-A(b) mice. To elucidate the role of the TCR and IFN-gamma/IL-12 signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg) expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and analyzed Th1 development of CD4(+) T cells from P25 TCR-Tg. Naive CD4(+) T cells from P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti-CD3. Naive CD4(+) T cells from P25 TCR-Tg preferentially develop Th1 cells upon Peptide-25 stimulation in the presence of I-A(b) splenic antigen-presenting cells under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4(+) T cells from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25 stimulation. Moreover, Peptide-25-loaded I-A(b)-transfected Chinese hamster ovary cells induce Th1 differentiation of naive CD4(+) T cells from P25 TCR-Tg in the absence of IFN-gamma or IL-12. These results imply that interaction between Peptide-25/I-A(b) and TCR may primarily influence determination of the fate of naive CD4(+) T cells in their differentiation towards the Th1 subset.