Early commitment of naive human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL-12
Early commitment of naive human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL-12
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DOI：
10.1038/icb.2009.64
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发表时间：
2009-11-01
影响因子：
4
通讯作者：
Tangye, Stuart G.
中科院分区：
文献类型：
--
作者：
Ma, Cindy S.;Suryani, Santi;Tangye, Stuart G.
滤泡辅助性T细胞（T-FH）是CD 4（+）T细胞的一个专门子集，定位于B细胞滤泡，在那里它们被定位为诱导最佳体液免疫应答提供帮助。T-FH细胞的关键特征是CXCR 5、ICOS、白细胞介素（IL）-21和BCL-6的表达。人类T-FH细胞发育的要求尚不清楚。在这里，我们表明IL-6，IL-12，IL-21和IL-23能够诱导从人扁桃体，外周血和脐带血中分离的初始CD 4（+）T细胞中IL-21的表达。然而，只有IL-12诱导这些活化的幼稚CD 4（+）T细胞上CXCR 5和ICOS的持续表达，并赋予它们为B细胞分化为免疫球蛋白分泌细胞提供增加的帮助的能力。IL-12的作用独立于干扰素-γ和T-bet，并且与BCL-6表达的上调相关。因此，这些细胞因子，特别是IL-12，可能在树突状细胞介导的初始CD 4（+）T细胞向T-FH细胞命运的引发过程中的早期阶段起作用，从而支持抗体介导的免疫。Immunology and Cell Biology（2009）87，590-600; doi：10.1038/icb.2009.64; 2009年9月1日在线发表
T follicular helper (T-FH) cells are a specialized subset of CD4(+) T cells that localize to B-cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of T-FH cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human T-FH cell development are unknown. Here we show that IL-6, IL-12, IL-21 and IL-23 are capable of inducing IL-21 expression in naive CD4(+) T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL-12 induced sustained expressions of CXCR5 and ICOS on these activated naive CD4(+) T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulin-secreting cells. The effects of IL-12 were independent of interferon-gamma and T-bet, and associated with upregulation of BCL-6 expression. Thus, these cytokines, particularly IL-12, are likely to act at an early stage during dendritic cell-mediated priming of naive CD4(+) T cells into a T-FH cell fate, and thus underpin antibody-mediated immunity. Immunology and Cell Biology (2009) 87, 590-600; doi: 10.1038/icb.2009.64; published online 1 September 2009