Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease
Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease
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DOI：
10.1038/415536a
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发表时间：
2002-01-31
期刊：
影响因子：
64.8
通讯作者：
Kuchroo, VK
中科院分区：
文献类型：
--
作者：
Monney, L;Sabatos, CA;Kuchroo, VK
初始CD 4（+）T辅助细胞的活化导致至少两种不同效应细胞群Th 1和Th 2细胞的发育（1-3）。Th 1细胞产生的细胞因子（干扰素（IFN）-γ、白细胞介素（IL）-2、肿瘤坏死因子（TNF）-α和α-光毒素）通常与细胞介导的抗细胞内病原体的免疫应答、迟发型超敏反应4和器官特异性自身免疫性疾病的诱导相关（5）。Th 2细胞产生细胞因子（IL-4、IL-10和IL-13），这些细胞因子对于控制细胞外蠕虫感染和促进特应性和过敏性疾病至关重要（4）。虽然对这两种辅助性T细胞亚群的功能了解很多，但很少有已知的表面分子区分它们（6）。我们在这里报告的跨膜蛋白，蒂姆-3，它包含一个免疫球蛋白和粘蛋白样结构域和分化的Th 1细胞上表达的识别和表征。Tim-3抗体的体内给药增强了实验性自身免疫性脑脊髓炎（EAE）（一种Th 1依赖性自身免疫性疾病）的临床和病理严重性，并增加了巨噬细胞的数量和活化水平。Tim-3可能通过调节巨噬细胞活化和/或功能在诱导自身免疫性疾病中起重要作用。
Activation of naive CD4(+) T-helper cells results in the development of at least two distinct effector populations, Th1 and Th2 cells(1-3). Th1 cells produce cytokines (interferon (IFN)-gamma, interleukin (IL)-2, tumour-necrosis factor (TNF)-alpha and lymphotoxin) that are commonly associated with cell-mediated immune responses against intracellular pathogens, delayed-type hypersensitivity reactions 4, and induction of organ-specific autoimmune diseases(5). Th2 cells produce cytokines (IL-4, IL-10 and IL-13) that are crucial for control of extracellular helminthic infections and promote atopic and allergic diseases(4). Although much is known about the functions of these two subsets of T-helper cells, there are few known surface molecules that distinguish between them(6). We report here the identification and characterization of a transmembrane protein, Tim-3, which contains an immunoglobulin and a mucin-like domain and is expressed on differentiated Th1 cells. In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages. Tim-3 may have an important role in the induction of autoimmune diseases by regulating macrophage activation and/or function.