Human Circulating PD-1⁺CXCR3^?CXCR5⁺ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses

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• 作者：Michela Locci ; Colin Havenar-Daughton ; Elise L ; ais ; Jennifer Wu ; Mark?A. Kroenke ; Cecilia?L. Arlehamn ; Laura?F. Su ; Rafael Cubas ; Mark?M. Davis ; Aless ; ro Sette ; Elias?K. Haddad ; International AIDS Vaccine Initiative Protocol C Principal Investigators ; Pascal Poignard ; Shane Crotty
• 刊名：Immunity
• 出版年：2013
• 出版时间：17 October, 2013
• 年：2013
• 卷：39
• 期：4
• 页码：758-769
• 全文大小：2293 K

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Summary

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.