Regulation and function of T1/ST2 expression on CD4+ T cells:: Induction of type 2 cytokine production by T1/ST2 cross-linking

Regulation and function of T1/ST2 expression on CD4+ T cells:: Induction of type 2 cytokine production by T1/ST2 cross-linking
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DOI:
10.4049/jimmunol.166.5.3143
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发表时间:
2001-03-01
影响因子:
4.4
通讯作者:
Kamradt, T
Kamradt, T
中科院分区:
医学2区
文献类型:
--
作者:
Meisel, C;Bonhagen, K;Kamradt, T

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孤儿受体T1/ST 2是IL-1 R家族的成员,优先表达于鼠Th 2细胞表面。本研究分析了体外培养的Th 2细胞上T1/ST 2表达的动力学和功能。而初始CD 4+细胞不表达T1/ST 2,大多数CD 4+细胞在Th 2极化条件下反复抗原刺激后变为T1/ST 2+。流式细胞仪分析表明,T1/ST 2表达的Th 2细胞的动力学延迟相比,2型细胞因子的产生的动力学。外源性IL-6、IL-5、IL-1和TNF-α增强Th 2细胞上T1/ST 2的表达,并且IL-6在这方面是迄今为止最有效的。然而,T1/ST 2的表达不依赖于IL-6的存在,并且在IL-6缺陷小鼠中也检测到。最重要的是,T1/ST 2的交联为Th 2而不是Th 1细胞提供了共刺激信号,并直接诱导增殖和2型细胞因子的产生。因此,T1/ST 2不仅是Th 2细胞的标志物,而且在Th 2细胞的活化中起重要作用。
wThe orphan receptor T1/ST2 a member of the IL-1R family, is preferentially expressed on the surface of murine Th2 cells. in this study, we analyzed the kinetics and function of T1/ST2 expression on Th2 cells in vitro. Whereas naive CD4+ cells did not express T1/ST2, most CD4+ cells became T1/ST2+ upon repeated antigenic stimulation under Th2-polarizing conditions. Flow cytometric analyses revealed that the kinetics of T1/ST2 expression on Th2 cells was delayed compared with the kinetics of type 2 cytokine production. Exogenous IL-6, IL-5, IL-1, and TNF-alpha enhanced the expression of T1/ST2 on Th2 cells, and IL-6 was by far most effective in this regard. However, the expression of T1/ST2 did not depend on the presence of IL-6 and was also detected in IL-6-deficient mice, Most important, cross-linking of T1/ST2 provided a costimulatory signal for Th2 but not Th1 cells and directly induced proliferation and type 2 cytokine production. Thus, T1/ST2 is not only a Th2 cell marker but also plays an important role in the activation of Th2 cells.