CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles
CXCR5+ follicular cytotoxic T cells control viral infection in B cell follicles
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DOI：
10.1038/ni.3543
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发表时间：
2016-10-01
影响因子：
30.5
通讯作者：
Yu, Di
中科院分区：
文献类型：
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作者：
Leong, Yew Ann;Chen, Yaping;Yu, Di
在未解决的感染过程中，一些病毒逃避免疫控制，并在某些细胞类型中建立持久的储存库，例如人类免疫缺陷病毒（HIV），它在滤泡辅助性T细胞（T - FH细胞）中持续存在，以及爱泼斯坦 - 巴尔病毒（EBV），它在B细胞中持续存在。在此，我们鉴定出一组特殊的细胞毒性T细胞（T - C细胞），它们表达趋化因子受体CXCR5，选择性地进入B细胞滤泡，并根除受感染的T - FH细胞和B细胞。这些细胞的分化（我们将其称为“滤泡细胞毒性T细胞”（T - FC细胞））需要转录因子Bcl6、E2A和TCF - 1，但受到转录调节因子Blimp1、Id2和Id3的抑制。Blimp1和E2A直接调节Cxcr5的表达，并与Bcl6和TCF - 1一起形成一个引导T - FC细胞发育的转录回路。T - FC细胞的鉴定对于制定控制针对B细胞和T - FH细胞的感染以及治疗B细胞源性恶性肿瘤的策略具有深远的意义。
During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (T-FH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (T-C cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (T-FC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided T-FC cell development. The identification of T-FC cells has far-reaching implications for the development of strategies to control infections that target B cells and T-FH cells and to treat B cell-derived malignancies.