The development and fate of follicular helper T cells defined by an IL-21 reporter mouse

The development and fate of follicular helper T cells defined by an IL-21 reporter mouse
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DOI:
10.1038/ni.2261
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发表时间:
2012-05-01
期刊:
影响因子:
30.5
通讯作者:
Nutt, Stephen L.
Nutt, Stephen L.
中科院分区:
医学1区
文献类型:
--
作者:
Luethje, Katja;Kallies, Axel;Nutt, Stephen L.

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老年中心需要CD4(+)滤泡辅助性T细胞(T-FH细胞),其标志是表达转录抑制因子Bcl-6、趋化因子受体CXCR5和白细胞介素21(IL-21)。为了跟踪T-FH细胞的发育和命运,我们通过将编码绿色荧光蛋白(GFP)的序列引入IL-21基因座来产生IL-21报告小鼠;这些小鼠在CD4(+)CXCR5(+)PD-1(+)T(FH)细胞中表达IL-21-GFP。IL-21-GFP(+)T-FH细胞是共表达几种细胞因子的多功能辅助细胞,包括干扰素-γ(IFN-γ)、IL-2和IL-4。T-FH细胞增殖并产生具有可塑性的可转移记忆细胞,其在回忆后分化为常规效应辅助T细胞和T-FH细胞。因此,我们证明了T-FH细胞不是终末分化的,而是保留了被招募到其他辅助性T细胞亚群和非淋巴组织中的灵活性。
Germinal centers require CD4(+) follicular helper T cells (T-FH cells), whose hallmark is expression of the transcriptional repressor Bcl-6, the chemokine receptor CXCR5 and interleukin 21 (IL-21). To track the development and fate of T-FH cells, we generated an IL-21 reporter mouse by introducing sequence encoding green fluorescent protein (GFP) into the Il21 locus; these mice had expression of IL-21-GFP in CD4(+)CXCR5(+)PD-1(+)T(FH) cells. IL-21-GFP(+) T-FH cells were multifunctional helper cells that coexpressed several cytokines, including interferon-gamma (IFN-gamma), IL-2 and IL-4. T-FH cells proliferated and gave rise to transferrable memory cells with plasticity, which differentiated after recall into conventional effector helper T cells and T-FH cells. Thus, we demonstrated that T-FH cells were not terminally differentiated but instead retained the flexibility to be recruited into other helper T cell subsets and nonlymphoid tissues.