Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses.
Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses.
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DOI：
10.1016/j.immuni.2013.08.031
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发表时间：
2013-10-17
期刊：
影响因子：
32.4
通讯作者：
Crotty S
中科院分区：
文献类型：
--
作者：
Locci M;Havenar-Daughton C;Landais E;Wu J;Kroenke MA;Arlehamn CL;Su LF;Cubas R;Davis MM;Sette A;Haddad EK;International AIDS Vaccine Initiative Protocol C Principal Investigators;Poignard P;Crotty S
目前获得许可的绝大多数人类疫苗都是以长期保护性抗体反应为基础的。鉴于在一些艾滋病毒感染者中发现了艾滋病毒广泛中和抗体(BNAbs)，现在可以想象到依赖抗体的艾滋病毒疫苗是可能的。然而，这些抗体很难开发，并且具有生发中心(GC)高度亲和力成熟的特征。CD4+T滤泡辅助细胞(TFH)是B细胞的特化细胞，也是GCs的必需细胞。因此，HIV bNAbs的形成可能依赖于TFH细胞。在这里，我们在正常人中鉴定了循环记忆PD-1+CXCR5+CD4+T细胞亚群，这些细胞是静息记忆细胞，通过基因表达谱、细胞因子谱和功能特性与真正的GC Tfh细胞关系最密切。重要的是，这些细胞的频率与大量HIV+人群中抗HIV的bNAbs的发展有关。
The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. It is now conceivable that an antibody-dependent HIV vaccine might be possible, given the discovery of HIV broadly neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these antibodies are difficult to develop and have characteristics indicative of a high degree of affinity maturation in germinal centers (GCs). CD4+ T follicular helper (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal individuals a subpopulation of circulating memory PD-1+CXCR5+ CD4+ T cells that are resting memory cells most related to bona fide GC Tfh cells by gene expression profile, cytokine profile, and functional properties. Importantly, the frequency of these cells correlated with the development of bnAbs against HIV in a large cohort of HIV+ individuals.
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发表时间：
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影响因子：
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通讯作者：
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