ICOS co-stimulatory receptor is essential for T-cell activation and function
ICOS co-stimulatory receptor is essential for T-cell activation and function
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DOI：
10.1038/35051100
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发表时间：
2001-01-04
期刊：
影响因子：
64.8
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Dong, C;Juedes, AE;Flavell, RA
T淋巴细胞的激活和免疫功能受共刺激分子的调节。CD28是B7基因产物的受体，在启动T细胞免疫反应中起主要作用(1，2)。CTLA4以更高的亲和力结合B7，在T细胞激活后被诱导，并参与下调T细胞反应(3，4)。可诱导共刺激分子(ICOS)是CD28/CTLA4家族的第三个成员，表达于活化的T细胞(5，6)。其配体B7H/B7RP-1在B细胞和动物注射脂多糖后的非免疫组织中表达(6，7)。为了了解ICOS在T细胞激活和功能中的作用，我们培育并分析了ICOS缺陷小鼠。在这里，我们发现在没有ICOS的情况下，T细胞的激活和增殖是有缺陷的。此外，ICOS-/-T细胞在体外分化或体内启动时不能产生白介素4。几种抗原免疫后的体液免疫反应需要ICOS。ICOS-/-小鼠对实验性自身免疫性脑脊髓炎的易感性显著增加，表明ICOS在炎症性自身免疫性疾病中具有保护作用。
T-lymphocyte activation and immune function are regulated by co-stimulatory molecules. CD28, a receptor for B7 gene products, has a chief role in initiating T-cell immune responses(1,2). CTLA4, which binds B7 with a higher affinity, is induced after T-cell activation and is involved in downregulating T-cell responses(3,4). The inducible co-stimulatory molecule (ICOS), a third member of the CD28/CTLA4 family, is expressed on activated T cells(5,6). Its ligand B7H/B7RP-1 is expressed on B cells and in non-immune tissues after injection of lipopolysaccharide into animals(6,7). To understand the role of ICOS in T-cell activation and function, we generated and analysed ICOS-deficient mice. Here we show that T-cell activation and proliferation are defective in the absence of ICOS. In addition, ICOS-/- T cells fail to produce interleukin-4 when differentiated in vitro or when primed in vivo. ICOS is required for humoral immune responses after immunization with several antigens. ICOS-/- mice showed greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that ICOS has a protective role in inflammatory autoimmune diseases.