Circulating HIV-Specific Interleukin-21+CD4+ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions

被引：107

作者：

Schultz, Bruce T. ^{[1
,2
,3
]}

Teigler, Jeffrey E. ^{[1
,2
]}

Pissani, Franco ^{[1
,2
]}

Oster, Alexander F. ^{[1
,2
]}

Kranias, Gregory ^{[1
,2
]}

Alter, Galit ^{[4
]}

Marovich, Mary ^{[1
,2
]}

Eller, Michael A. ^{[1
,2
]}

Dittmer, Ulf ^{[5
]}

Robb, Merlin L. ^{[1
,2
]}

Kim, Jerome H. ^{[1
,6
]}

Michael, Nelson L. ^{[1
]}

Bolton, Diane ^{[1
,2
]}

Streeck, Hendrik ^{[1
,2
,3
]}

机构：

[1] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA

[2] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA

[3] Univ Duisburg Essen, Univ Hosp Essen, Inst HIV Res, D-45147 Essen, Germany

[4] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[5] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, D-45147 Essen, Germany

[6] Int Vaccine Inst, Seoul 151742, South Korea

来源：

IMMUNITY | 2016年 / 44卷 / 01期

关键词：

ANTIBODY-RESPONSES; DIFFERENTIATION; IL-21; PROLIFERATION; INDUCTION; INFECTION; CYTOKINE; DYNAMICS;

D O I：

10.1016/j.immuni.2015.12.011

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：

A central effort in HIV vaccine development is to generate protective broadly neutralizing antibodies, a process dependent on T follicular helper (Tfh) cells. The feasibility of using peripheral blood counterparts of lymph node Tfh cells to assess the immune response and the influence of viral and vaccine antigens on their helper functions remain obscure. We assessed circulating HIV-specific IL-21(+) CD4(+) T cells and showed transcriptional and phenotypic similarities to lymphoid Tfh cells, and hence representing peripheral Tfh (pTfh) cells. pTfh cells were functionally active and B cell helper quality differed depending on antigen specificity. Furthermore, we found higher frequency of pTfh cells in peripheral blood mononuclear cell specimens from the ALVAC+AIDSVAX (RV144) HIV vaccine trial associated with protective antibody responses compared to the non-protective DNA+Ad5 vaccine trial. Together, we identify IL-21(+) CD4(+) T cells as pTfh cells, implicating them as key populations in the generation of vaccine-evoked antibody responses.

引用

页码：167 / 178

页数：12

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