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

Bruce T Schultz; Jeffrey E Teigler; Franco Pissani; Alexander F Oster; Gregory Kranias; Galit Alter; Mary Marovich; Michael A Eller; Ulf Dittmer; Merlin L Robb; Jerome H Kim; Nelson L Michael; Diane Bolton; Hendrik Streeck

doi:10.1016/j.immuni.2015.12.011

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

Immunity. 2016 Jan 19;44(1):167-178. doi: 10.1016/j.immuni.2015.12.011. Epub 2016 Jan 12.

Authors

Affiliations

¹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
² U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
⁴ Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; International Vaccine Institute, Seoul 151-742, Korea.
⁶ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁷ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. Electronic address: hendrik.streeck@uk-essen.de.

PMID: 26795249
DOI: 10.1016/j.immuni.2015.12.011

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Separation
Enzyme-Linked Immunospot Assay
Flow Cytometry
HIV Infections / immunology*
HIV-1 / immunology
Humans
Interleukins / immunology*
Real-Time Polymerase Chain Reaction
T-Lymphocyte Subsets / immunology*
T-Lymphocytes, Helper-Inducer / immunology*

Substances

Interleukins
interleukin-21

Abstract

Publication types

MeSH terms

Substances

Grants and funding