@article{8f6ae47b303947cba160176471a232e8,
title = "Circulating HIV-Specific Interleukin-21+CD4+ T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions",
abstract = "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.",
author = "Schultz, {Bruce T.} and Teigler, {Jeffrey E.} and Franco Pissani and Oster, {Alexander F.} and Gregory Kranias and Galit Alter and Mary Marovich and Eller, {Michael A.} and Ulf Dittmer and Robb, {Merlin L.} and Kim, {Jerome H.} and Michael, {Nelson L.} and Diane Bolton and Hendrik Streeck",
note = "Funding Information: We would like to thank Dr. Madelene Lindqvist and Dr. Jan van Lunzen for their help with the manuscript. This work was funded by the U.S. NIH (R01 AI091450-01 and R01 AI094602-01) and a cooperative agreement (W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). The reagents HIV-1 PTE Gag and Env Peptides were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH; human rIL-2 was from Dr. Maurice Gately, Hoffmann at La Roche Inc. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. Funding Information: We would like to thank Dr. Madelene Lindqvist and Dr. Jan van Lunzen for their help with the manuscript. This work was funded by the U.S. NIH ( R01 AI091450-01 and R01 AI094602-01 ) and a cooperative agreement ( W81XWH-11-2-0174 ) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD) . The reagents HIV-1 PTE Gag and Env Peptides were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH; human rIL-2 was from Dr. Maurice Gately, Hoffmann at La Roche Inc. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jan,
day = "19",
doi = "10.1016/j.immuni.2015.12.011",
language = "English",
volume = "44",
pages = "167--178",
journal = "Immunity",
issn = "1074-7613",
number = "1",
}