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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Inadequate T follicular cell help impairs B cell immunity during HIV infection
Nature medicine, v 19(4), pp 494-499
01 Apr 2013
PMID: 23475201
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations(1-3). We report here that even though there is an expansion of follicular helper T (T-FH) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. We found a higher frequency of programmed cell death ligand 1 (PD-L1)(+) germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1-PD-L1 interaction in regulating T-FH cell function. In fact, we show that engagement of PD-1 on T-FH cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. Blocking PD-1 signaling enhances HIV-specific immunoglobulin production in vitro. We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro. Our results suggest that deregulation of T-FH cell-mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on T-FH cells. These results demonstrate a role for T-FH cell impairment in HIV pathogenesis and suggest that enhancing their function could have a major impact on the outcome and control of HIV infection, preventing future infections and improving immune responses to vaccinations.
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Details
- Title
- Inadequate T follicular cell help impairs B cell immunity during HIV infection
- Creators
- Rafael A. Cubas - Vaccine & Gene Therapy Institute of FloridaJoseph C. Mudd - Case Western Reserve UniversityAnne-Laure Savoye - University of LausanneMatthieu Perreau - University of LausanneJulien van Grevenynghe - Vaccine & Gene Therapy Institute of FloridaTalibah Metcalf - Vaccine & Gene Therapy Institute of FloridaElizabeth Connick - University of DenverAmie Meditz - University of DenverGordon J. Freeman - Harvard University ,Guillermo Abesada-Terk - Memorial Health SystemJeffrey M. Jacobson - Drexel UniversityAri D. Brooks - Drexel UniversityShane Crotty - La Jolla Institute For Allergy & ImmunologyJacob D. Estes - Science Applications International CorporationGiuseppe Pantaleo - University of LausanneMichael M. Lederman - Case Western Reserve UniversityElias K. Haddad - Vaccine & Gene Therapy Institute of Florida
- Publication Details
- Nature medicine, v 19(4), pp 494-499
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- AI 76174 / Cleveland Immunopathogenesis Consortium AI 36219 / Case Western Reserve University Center for AIDS Research HHSN272201100017C; NIH-1P01 AI080192; U19AI082630; 2P01 AI056299; R01 AI096966 / US National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01AI076174 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine); Surgery
- Web of Science ID
- WOS:000317109100036
- Scopus ID
- 2-s2.0-84878454838
- Other Identifier
- 991019167326504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Medicine, Research & Experimental