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

被引：692

作者：

Locci, Michela ^{[1
,2
]}

Havenar-Daughton, Colin ^{[1
,2
]}

Landais, Elise

Wu, Jennifer ^{[1
]}

Kroenke, Mark A. ^{[1
]}

Arlehamn, Cecilia L. ^{[1
]}

Su, Laura F. ^{[6
,7
]}

Cubas, Rafael ^{[8
]}

Davis, Mark M. ^{[6
,7
]}

Sette, Alessandro ^{[1
]}

Haddad, Elias K.

Poignard, Pascal ^{[4
,5
]}

Crotty, Shane ^{[1
,2
,3
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92037 USA

[3] Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[4] Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[6] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94304 USA

[7] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94304 USA

[8] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA

[9] Int AIDS Vaccine Initiat, New York, NY 10038 USA

来源：

IMMUNITY | 2013年 / 39卷 / 04期

关键词：

T-FOLLICULAR HELPER; B-CELLS; EXPRESSION; BCL6; LYMPHOCYTES; COMMITMENT; REGULATORS; PROTECTION; DYNAMICS; PROGRAM;

D O I：

10.1016/j.immuni.2013.08.031

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：758 / 769

页数：12

共 52 条

[1]

The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells [J].