循环前体 CCR7(lo)PD-1(hi)CXCR5⁺CD4⁺T 细胞表明滤泡辅助性 T 细胞（Tfh 细胞）活性，并在再次暴露抗原时促进抗体应答。
Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure.
机构信息
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China.
出版信息
Immunity. 2013 Oct 17;39(4):770-81. doi: 10.1016/j.immuni.2013.09.007.
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 antibody 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.
滤泡辅助 T（Tfh）细胞支持高亲和力和长期抗体应答。在这里，我们发现，在人和小鼠循环的 CXCR5⁺CD4⁺T 细胞中，CCR7（低）PD-1（高）亚群具有部分 Tfh 效应细胞表型，而 CCR7（高）PD-1（低）细胞具有静止表型。循环 CCR7（低）PD-1（高）亚群表明淋巴器官中 Tfh 分化活跃，并与自身免疫性疾病的临床指标相关。因此，CCR7（低）PD-1（高）亚群提供了一个生物标志物，可用于监测感染或接种疫苗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。CCR7（高）PD-1（低）和 CCR7（低）PD-1（高）亚群的分化都需要 ICOS 和 BCL6，但不需要 SAP，这表明循环的 CXCR5⁺辅助 T 细胞主要是在生发中心之前产生的。再次遇到抗原时，CCR7（低）PD-1（高）CXCR5⁺前体细胞迅速分化为成熟的 Tfh 细胞，以促进抗体应答。因此，循环的 CCR7（低）PD-1（高）CXCR5⁺CD4⁺T 细胞是在 Tfh 分化活跃时产生的，代表了一种新的免疫早期记忆机制。
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