Circulating Precursor CCR7loPD-1hi CXCR5+ CD4+ T Cells Indicate Tfh Cell Activity and Promote Antibody Responses upon Antigen Reexposure
Circulating Precursor CCR7loPD-1hi CXCR5+ CD4+ T Cells Indicate Tfh Cell Activity and Promote Antibody Responses upon Antigen Reexposure
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DOI：
10.1016/j.immuni.2013.09.007
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发表时间：
2013-10-17
期刊：
影响因子：
32.4
通讯作者：
Yu, Di
中科院分区：
文献类型：
--
作者：
He, Jing;Tsai, Louis M.;Yu, Di
滤泡B辅助T（Tfh）细胞支持高亲和力和长期抗体应答。我们发现在人和小鼠的循环CXCR 5（+）CD 4（+）T细胞中，CCR 7（lo）PD-1（hi）亚群具有部分Tfh效应子表型，而CCR 7（hi）PD-1（lo）细胞具有静息表型。循环CCR 7（lo）PD-1（hi）亚群指示淋巴器官中的活性Tfh分化，并且与自身免疫性疾病的临床指标相关。因此，CCR 7（lo）PD-1（hi）亚群提供了一种生物标志物，用于监测感染或疫苗接种期间的保护性抗体应答以及自身免疫性疾病中的致病性抗体应答。CCR 7（hi）PD-1（lo）和CCR 7（lo）PD-1（hi）亚群的分化都需要ICOS和BCL 6，但不需要SAP，这表明循环中的CXCR 5（+）辅助T细胞主要在生殖中心之前产生。在抗原再次相遇时，CCR 7（lo）PD-1（hi）CXCR 5（+）前体迅速分化成成熟的Tfh细胞以促进抗体应答。因此，循环CCR 7（lo）PD-1（hi）CXCR 5（+）CD 4（+）T细胞在活性Tfh分化期间产生，并且代表免疫早期记忆的新机制。
Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5(+) CD4(+) T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi) PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5(+) helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5(+) precursors rapidly differentiate into mature Tfh cells to promote anti-body responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.