Interferon gamma signaling alters the function of T helper type 1 cells.
Interferon gamma signaling alters the function of T helper type 1 cells.
复制标题
干扰素伽马信号传导改变T辅助1型细胞的功能。
DOI：
10.1084/jem.192.7.977
复制
发表时间：
2000-10-02
影响因子：
15.3
通讯作者：
Rothman, P B
中科院分区：
文献类型：
--
作者：
Tau, G Z;von der Weid, T;Lu, B;Cowan, S;Kvatyuk, M;Pernis, A;Cattoretti, G;Braunstein, N S;Coffman, R L;Rothman, P B
调节不同辅助性T（Th）细胞亚群响应细胞因子的能力的一种机制是细胞因子受体的差异表达。例如，Th 2细胞表达干扰素γ受体（IFN-γR）的两条链，而Th 1细胞不表达IFN-γR的第二条链（IFN-γR2），因此对IFN-γ无应答。为了确定IFN-γR2表达的调节以及由此产生的IFN-γ应答性对于初始CD 4 + T细胞分化为Th 1细胞或对于Th 1效应子功能是否重要，我们产生了其中IFN-γR2的转基因（TG）表达由CD 2启动子和增强子控制的小鼠。来自IFN-γR2 TG小鼠的CD 4 + T细胞在体外表现出受损的Th 1极化电位。TG小鼠在体内也表现出Th 1依赖性免疫的几种缺陷，包括减弱的迟发型超敏反应和抗原特异性IFN-γ产生减少。此外，TG小鼠对利什曼原虫的Th 1应答受损，表现为寄生虫血症增加和比野生型同窝仔更严重的病变。总之，这些数据表明IFN-γR2的持续表达抑制Th 1分化和功能。因此，在Th 1细胞中获得IFN-γ无应答表型在这些细胞的发育和功能中起着至关重要的作用。
One mechanism regulating the ability of different subsets of T helper (Th) cells to respond to cytokines is the differential expression of cytokine receptors. For example, Th2 cells express both chains of the interferon γ receptor (IFN-γR), whereas Th1 cells do not express the second chain of the IFN-γR (IFN-γR2) and are therefore unresponsive to IFN-γ. To determine whether the regulation of IFN-γR2 expression, and therefore IFN-γ responsiveness, is important for the differentiation of naive CD4+ T cells into Th1 cells or for Th1 effector function, we generated mice in which transgenic (TG) expression of IFN-γR2 is controlled by the CD2 promoter and enhancer. CD4+ T cells from IFN-γR2 TG mice exhibit impaired Th1 polarization potential in vitro. TG mice also display several defects in Th1-dependent immunity in vivo, including attenuated delayed-type hypersensitivity responses and decreased antigen-specific IFN-γ production. In addition, TG mice mount impaired Th1 responses against Leishmania major, as manifested by increased parasitemia and more severe lesions than their wild-type littermates. Together, these data suggest that the sustained expression of IFN-γR2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-γ–unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.