Standard

Production of HIV-1 env-specific antibodies mediating innate immune functions depends on cognate interleukin-21-secreting CD4+T cells. / Pušnik, Jernej; Fischinger, Stephanie; Dittmer, Ulf et al.

In: Journal of virology, Vol. 95, No. 8, e02097, 01.04.2021.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

APA

Vancouver

Author

Pušnik, Jernej ; Fischinger, Stephanie ; Dittmer, Ulf et al. / Production of HIV-1 env-specific antibodies mediating innate immune functions depends on cognate interleukin-21-secreting CD4+T cells. In: Journal of virology. 2021 ; Vol. 95, No. 8.

BibTeX

@article{2b592a670d9347b99ca209ec4ce3b8c1,
title = "Production of HIV-1 env-specific antibodies mediating innate immune functions depends on cognate interleukin-21-secreting CD4+T cells",
abstract = "Antibodies with a functional Fc region were previously associated with protection from HIV-1 acquisition and spontaneous suppression of viral replication. Unlike broadly neutralizing antibodies, they are not restricted to neutralizing epitopes and do not require unconventional structural traits to exert their antiviral activity. They therefore develop earlier after infection and can be detected in the majority of cases. The conditions under which these antibodies are generated, however, remain largely unknown. Here, we demonstrate that the generation of HIV-1 Env-specific antibodies facilitating Fc-dependent innate immune responses, including neutrophil phagocytosis (ADNP), complement deposition (ADCD), and NK cell activation, likely depends on help provided by CD4+ T and peripheral T follicular helper (pTfh) cells secreting interleukin- 21 (IL-21). Other proteins, including CD40L, gamma interferon (IFN-g), and IL-4/13, involved in cross talk between B and T cells were linked to the production of antibodies with a functional Fc region but only when coexpressed with IL-21. As a potential source of these antibodies, we identified a subset of Env-specific memory B cells known to be expanded in chronic HIV-1 infection. The frequency and level of Blimp-1 expression in Env-specific tissue-like memory B cells (TLM) correlated with the functional CD4+ T cell subsets associated with robust antibody-dependent innate responses. Thus, our data suggest a mechanism responsible for the generation of antibodies with functional Fc region in chronically HIV-1-infected individuals that is based on CD4+ T cell-induced activation of memory B cells.",
keywords = "ADCD, ADNP, Antibody, CD4T cells, Env, HIV-1, IL-21, NK cell activation, PTfh, TLM",
author = "Jernej Pu{\v s}nik and Stephanie Fischinger and Ulf Dittmer and Stefan Esser and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Galit Alter and Hendrik Streeck",
note = "Funding Information: Financial support for this study was provided by the German research association Deutsche Forschungsgemeinschaft (DFG) through the research training group Graduiertenkolleg 1949/2, entitled Immunantwort in Infektionskrankheiten—Regulation zwischen angeborener und erworbener Immunit{\"a}t. We declare no competing financial interests. Publisher Copyright: Copyright {\textcopyright} 2021 American Society for Microbiology. All Rights Reserved.",
year = "2021",
month = apr,
day = "1",
doi = "10.1128/JVI.02097-20",
language = "English",
volume = "95",
journal = "Journal of virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

RIS

TY - JOUR

T1 - Production of HIV-1 env-specific antibodies mediating innate immune functions depends on cognate interleukin-21-secreting CD4+T cells

AU - Pušnik, Jernej

AU - Fischinger, Stephanie

AU - Dittmer, Ulf

AU - Esser, Stefan

AU - van Gils, Marit J.

AU - Sanders, Rogier W.

AU - Alter, Galit

AU - Streeck, Hendrik

N1 - Funding Information: Financial support for this study was provided by the German research association Deutsche Forschungsgemeinschaft (DFG) through the research training group Graduiertenkolleg 1949/2, entitled Immunantwort in Infektionskrankheiten—Regulation zwischen angeborener und erworbener Immunität. We declare no competing financial interests. Publisher Copyright: Copyright © 2021 American Society for Microbiology. All Rights Reserved.

PY - 2021/4/1

Y1 - 2021/4/1

N2 - Antibodies with a functional Fc region were previously associated with protection from HIV-1 acquisition and spontaneous suppression of viral replication. Unlike broadly neutralizing antibodies, they are not restricted to neutralizing epitopes and do not require unconventional structural traits to exert their antiviral activity. They therefore develop earlier after infection and can be detected in the majority of cases. The conditions under which these antibodies are generated, however, remain largely unknown. Here, we demonstrate that the generation of HIV-1 Env-specific antibodies facilitating Fc-dependent innate immune responses, including neutrophil phagocytosis (ADNP), complement deposition (ADCD), and NK cell activation, likely depends on help provided by CD4+ T and peripheral T follicular helper (pTfh) cells secreting interleukin- 21 (IL-21). Other proteins, including CD40L, gamma interferon (IFN-g), and IL-4/13, involved in cross talk between B and T cells were linked to the production of antibodies with a functional Fc region but only when coexpressed with IL-21. As a potential source of these antibodies, we identified a subset of Env-specific memory B cells known to be expanded in chronic HIV-1 infection. The frequency and level of Blimp-1 expression in Env-specific tissue-like memory B cells (TLM) correlated with the functional CD4+ T cell subsets associated with robust antibody-dependent innate responses. Thus, our data suggest a mechanism responsible for the generation of antibodies with functional Fc region in chronically HIV-1-infected individuals that is based on CD4+ T cell-induced activation of memory B cells.

AB - Antibodies with a functional Fc region were previously associated with protection from HIV-1 acquisition and spontaneous suppression of viral replication. Unlike broadly neutralizing antibodies, they are not restricted to neutralizing epitopes and do not require unconventional structural traits to exert their antiviral activity. They therefore develop earlier after infection and can be detected in the majority of cases. The conditions under which these antibodies are generated, however, remain largely unknown. Here, we demonstrate that the generation of HIV-1 Env-specific antibodies facilitating Fc-dependent innate immune responses, including neutrophil phagocytosis (ADNP), complement deposition (ADCD), and NK cell activation, likely depends on help provided by CD4+ T and peripheral T follicular helper (pTfh) cells secreting interleukin- 21 (IL-21). Other proteins, including CD40L, gamma interferon (IFN-g), and IL-4/13, involved in cross talk between B and T cells were linked to the production of antibodies with a functional Fc region but only when coexpressed with IL-21. As a potential source of these antibodies, we identified a subset of Env-specific memory B cells known to be expanded in chronic HIV-1 infection. The frequency and level of Blimp-1 expression in Env-specific tissue-like memory B cells (TLM) correlated with the functional CD4+ T cell subsets associated with robust antibody-dependent innate responses. Thus, our data suggest a mechanism responsible for the generation of antibodies with functional Fc region in chronically HIV-1-infected individuals that is based on CD4+ T cell-induced activation of memory B cells.

KW - ADCD

KW - ADNP

KW - Antibody

KW - CD4T cells

KW - Env

KW - HIV-1

KW - IL-21

KW - NK cell activation

KW - PTfh

KW - TLM

UR - http://www.scopus.com/inward/record.url?scp=85104139220&partnerID=8YFLogxK

U2 - 10.1128/JVI.02097-20

DO - 10.1128/JVI.02097-20

M3 - Article

C2 - 33504598

VL - 95

JO - Journal of virology

JF - Journal of virology

SN - 0022-538X

IS - 8

M1 - e02097

ER -

ID: 17944393