Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development:: roles of T-cell receptor-mediated signals
Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development:: roles of T-cell receptor-mediated signals
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DOI：
10.1111/j.1365-2567.2007.02630.x
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发表时间：
2007-10-01
期刊：
影响因子：
6.4
通讯作者：
Takatsu, Kiyoshi
中科院分区：
文献类型：
--
作者：
Ariga, Haruyuki;Shimohakamada, Yoko;Takatsu, Kiyoshi
使用T细胞受体（TCR）转基因小鼠，我们证明了初始CD 4（+）T细胞的TCR刺激诱导瞬时T-bet表达、白细胞介素（IL）-12受体β 2上调和加塔-3下调，这导致T辅助细胞（Th）1分化，即使在不存在干扰素-γ的情况下用负载肽的I-A（B）-转染的中国仓鼠卵巢细胞刺激细胞时也是如此（IFN-γ）和IL-12。持续的IFN-γ和IL-12刺激增强幼稚T细胞分化为Th 1细胞。有趣的是，即使在不存在IFN-γ或IL-12的情况下通过TCR刺激T-bet（-/-）初始CD 4（+）T细胞，也观察到显著的Th 1应答。在不存在IFN-γ或IL-12的情况下，用改变的肽配体（其对TCR的亲合力低于原始肽的亲合力）刺激初始CD 4（+）T细胞不能上调瞬时T-bet表达，维持加塔-3表达，并诱导分化为Th 2细胞。这些结果支持了这样的观点，即TCR和负载肽的抗原呈递细胞之间的直接相互作用，即使在T-bet表达和共刺激信号不存在的情况下，也主要决定了初始CD 4（+）T细胞向Th 1细胞的命运。
Using T-cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4(+) T cells induces transient T-bet expression, interleukin (IL)-12 receptor beta 2 up-regulation, and GATA-3 down-regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide-loaded I-A(b)-transfected Chinese hamster ovary cells in the absence of interferon-gamma (IFN-gamma) and IL-12. Sustained IFN-gamma and IL-12 stimulation augments naive T-cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T-bet(-/-) naive CD4(+) T cells are stimulated through TCR in the absence of IFN-gamma or IL-12. Stimulation of naive CD4(+) T cells in the absence of IFN-gamma or IL-12 with altered peptide ligand, whose avidity to the TCR is lower than that of original peptide, fails to up-regulate transient T-bet expression, sustains GATA-3 expression, and induces differentiation into Th2 cells. These results support the notion that direct interaction between TCR and peptide-loaded antigen-presenting cells, even in the absence of T-bet expression and costimulatory signals, primarily determine the fate of naive CD4(+) T cells to Th1 cells.