Expression of ICOS in vivo defines CD4+ effector T cells with high inflammatory potential and a strong bias for secretion of interleukin 10
Expression of ICOS in vivo defines CD4+ effector T cells with high inflammatory potential and a strong bias for secretion of interleukin 10
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DOI：
10.1084/jem.20020632
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发表时间：
2003-01-20
影响因子：
15.3
通讯作者：
Kroczek, RA
中科院分区：
文献类型：
--
作者：
Löhning, M;Hutloff, A;Kroczek, RA
到目前为止进行的研究分析了可诱导共刺激分子(ICOS)在模型疾病中的总体参与，但没有提供体内表达ICOS的T细胞的性质和功能的信息。我们在由环境抗原塑造的“无偏见”免疫系统的背景下，检测了未经操作的小鼠次级淋巴器官中的ICOS+T细胞。通过单细胞分析，发现ICOSlow细胞与早期细胞因子IL-2、IL-3、IL-6和干扰素(干扰素)-γ有松散的相关性。ICOS中等细胞是体内ICOS T细胞的主要来源，与Th2类细胞因子IL-4、IL-5和IL-13的合成密切相关，在体内表现出较强的炎症效应。相比之下，ICOSHigh T细胞与抗炎细胞因子IL-10高度和选择性地联系在一起。总体而言，这些数据似乎表明，ICOS细胞表面密度作为一种调节机制，释放具有不同免疫学特性的细胞因子。进一步的体外激活T细胞体内功能实验有力地表明，尽管ICOS+群体只占体内携带早期或晚期激活标记的T细胞的10%左右，但实际上涵盖了所有效应性T细胞，这一发现具有重要的诊断和治疗意义。
The studies performed to date analyzed the overall participation of the inducible costimulator (ICOS) in model diseases, but did not yield information on the nature and function of ICOS-expressing T cells in vivo. We examined ICOS+ T cells in the secondary lymphoid organs of nonmanipulated mice, in the context of an "unbiased" immune system shaped by environmental antigens. Using single cell analysis, ICOSlow cells were found to be loosely associated with the early cytokines interleukin (IL)-2, IL-3, IL-6, and interferon (IFN)-gamma. ICOSmedium cells, the large majority of ICOS' T cells in vivo, were very tightly associated with the synthesis of the T helper type 2 (Th2) cytokines IL-4, IL-5, and IL-13, and these cells exhibited potent inflammatory effects in vivo. In contrast, ICOShigh T cells were highly and selectively linked to the anti-inflammatory cytokine IL-10. Overall, these data seem to indicate that ICOS cell surface density serves as a regulatory mechanism for the release of cytokines with different immunological properties. Further in vivo functional experiments with in vitro-activated T cells strongly suggested that the ICOS+ population, although representing in vivo only around 10% of T cells bearing early or late activation markers, nevertheless encompasses virtually all effector T cells, a finding with major diagnostic and therapeutic implications.