TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis.

TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis.
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TSLP和IL-7使用两种不同的机制来调节人CD4+ T细胞稳态。

DOI:
10.1084/jem.20090153
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发表时间:
2009-09-28
影响因子:
15.3
通讯作者:
Liu, Yong-Jun
Liu, Yong-Jun
中科院分区:
医学1区
文献类型:
--
作者:
Lu, Ning;Wang, Yi-Hong;Wang, Yui-Hsi;Arima, Kazuhiko;Hanabuchi, Shino;Liu, Yong-Jun

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胸腺基质淋巴生成素(TSLP)是否能直接诱导人类CD4+T细胞增殖和Th2分化尚不清楚。我们报道,与髓系树突状细胞(MDCs)相比,静息和激活的CD4+T细胞表达高水平的IL-7受体α链,但表达非常低的TSLP受体(TSLPR)。免疫组织学和流式细胞仪分析证实了这一点,在活体中,只有具有更多激活表型的MDCs亚群在人类扁桃体中表达TSLPR。IL-7诱导STAT1、-3和-5的强激活,并在抗CD3和抗CD28的单抗存在下促进初始的CD4+T细胞的增殖,而TSLP诱导弱的STAT5激活,与微弱的促进细胞存活和增殖有关,但不能诱导细胞的扩增和Th2的分化。只有当分离的原始CD4+T细胞与低至0.5%的MDCS共同培养时,TSLP才能观察到促进强大的人T细胞增殖的作用。TSLP只能在同种异体MDCS存在的情况下诱导初始的CD4+T细胞分化为Th2细胞。这些结果表明,IL-7和TSLP通过不同的机制来调节人类CD4+T细胞的动态平衡。
Whether thymic stromal lymphopoietin (TSLP) directly induces potent human CD4+ T cell proliferation and Th2 differentiation is unknown. We report that resting and activated CD4+ T cells expressed high levels of IL-7 receptor a chain but very low levels of TSLP receptor (TSLPR) when compared with levels expressed in myeloid dendritic cells (mDCs). This was confirmed by immunohistology and flow cytometry analyses showing that only a subset of mDCs, with more activated phenotypes, expressed TSLPR in human tonsils in vivo. IL-7 induced strong STAT1, -3, and -5 activation and promoted the proliferation of naive CD4+ T cells in the presence of anti-CD3 and anti-CD28 monoclonal antibodies, whereas TSLP induced weak STAT5 activation, associated with marginally improved cell survival and proliferation, but failed to induce cell expansion and Th2 differentiation. The effect of TSLP on enhancing strong human T cell proliferation was observed only when sorted naive CD4+ T cells were cultured with mDCs at levels as low as 0.5%. TSLP could only induce naive CD4+ T cells to differentiate into Th2 cells in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP use different mechanisms to regulate human CD4+ T cell homeostasis.
DOI: 10.1084/jem.20062211
发表时间: 2007-02-19
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影响因子: --
作者:
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发表时间: 2004-04-01
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影响因子: 30.5
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