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首页> 外文期刊>Nature immunology >CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles
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CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles

机译:CXCR5(+)滤泡细胞毒性T细胞控制B细胞滤泡中的病毒感染

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摘要

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.
机译:在未解决的感染过程中,某些病毒会逃避免疫控制,并在某些细胞类型中建立持久性储库,例如人类免疫缺陷病毒(HIV)和卵泡辅助性T细胞(T-FH细胞)和爱泼斯坦-巴尔病毒(EBV) ,它持续存在于B细胞中。在这里,我们确定了一组专门的细胞毒性T细胞(T-C细胞),它们表达趋化因子受体CXCR5,选择性进入B细胞滤泡,并消除了感染的TFH细胞和B细胞。这些细胞的分化,我们称为“卵泡细胞毒性T细胞”(T-FC细胞),需要转录因子Bcl6,E2A和TCF-1,但受到转录调节剂Blimp1,Id2和Id3的抑制。 Blimp1和E2A直接调节Cxcr5的表达,并与Bcl6和TCF-1一起形成转录电路,指导T-FC细胞的发育。 T-FC细胞的鉴定对控制针对B细胞和T-FH细胞的感染以及治疗B细胞来源的恶性肿瘤的策略发展具有深远的意义。

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