The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection

Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and...

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Main Authors: Alessandra Noto, Madeleine Suffiotti, Victor Joo, Antonio Mancarella, Francesco A. Procopio, Guy Cavet, Yvonne Leung, Jean-Marc Corpataux, Matthias Cavassini, Agostino Riva, Leonidas Stamatatos, Raphael Gottardo, Adrian B. McDermott, Richard A. Koup, Craig Fenwick, Matthieu Perreau, Giuseppe Pantaleo
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.960120/full
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author Alessandra Noto
Madeleine Suffiotti
Victor Joo
Antonio Mancarella
Francesco A. Procopio
Guy Cavet
Yvonne Leung
Jean-Marc Corpataux
Matthias Cavassini
Agostino Riva
Leonidas Stamatatos
Raphael Gottardo
Adrian B. McDermott
Richard A. Koup
Craig Fenwick
Matthieu Perreau
Giuseppe Pantaleo
Giuseppe Pantaleo
author_facet Alessandra Noto
Madeleine Suffiotti
Victor Joo
Antonio Mancarella
Francesco A. Procopio
Guy Cavet
Yvonne Leung
Jean-Marc Corpataux
Matthias Cavassini
Agostino Riva
Leonidas Stamatatos
Raphael Gottardo
Adrian B. McDermott
Richard A. Koup
Craig Fenwick
Matthieu Perreau
Giuseppe Pantaleo
Giuseppe Pantaleo
author_sort Alessandra Noto
collection DOAJ
description Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3- Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3- Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3+ Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3+ B cells showed lower rate of somatic hypermutation, as compared to CXCR3- B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.
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spelling doaj.art-f7bc6d2291a744dca296140e03ea8ac72022-12-22T02:17:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.960120960120The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infectionAlessandra Noto0Madeleine Suffiotti1Victor Joo2Antonio Mancarella3Francesco A. Procopio4Guy Cavet5Yvonne Leung6Jean-Marc Corpataux7Matthias Cavassini8Agostino Riva9Leonidas Stamatatos10Raphael Gottardo11Adrian B. McDermott12Richard A. Koup13Craig Fenwick14Matthieu Perreau15Giuseppe Pantaleo16Giuseppe Pantaleo17Service Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandAtreca, Redwood City, CA, United StatesAtreca, Redwood City, CA, United StatesService of Vascular Surgery, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService of Infectious Diseases, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandDivision of Infectious Diseases, Luigi Sacco Hospital, University of Milan, Milan, ItalyDepartment of Global Health, Seattle University of Washington, Seattle, WA, United StatesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandService Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandSwiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, SwitzerlandOptimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3- Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3- Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3+ Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3+ B cells showed lower rate of somatic hypermutation, as compared to CXCR3- B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.960120/fulllymph nodesfollicular T helper cellsgerminal center B cells (GC B cells)HIV-1 infectionT helper cell
spellingShingle Alessandra Noto
Madeleine Suffiotti
Victor Joo
Antonio Mancarella
Francesco A. Procopio
Guy Cavet
Yvonne Leung
Jean-Marc Corpataux
Matthias Cavassini
Agostino Riva
Leonidas Stamatatos
Raphael Gottardo
Adrian B. McDermott
Richard A. Koup
Craig Fenwick
Matthieu Perreau
Giuseppe Pantaleo
Giuseppe Pantaleo
The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
Frontiers in Immunology
lymph nodes
follicular T helper cells
germinal center B cells (GC B cells)
HIV-1 infection
T helper cell
title The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
title_full The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
title_fullStr The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
title_full_unstemmed The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
title_short The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
title_sort deficiency in th2 like tfh cells affects the maturation and quality of hiv specific b cell response in viremic infection
topic lymph nodes
follicular T helper cells
germinal center B cells (GC B cells)
HIV-1 infection
T helper cell
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.960120/full
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