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Journal article
Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection
The Journal of immunology (1950), Vol.195(12), pp.5625-5636
15 Dec 2015
PMCID: PMC4670798
PMID: 26546609
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2-responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART.
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- Title
- Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection
- Creators
- Rafael Cubas - Vaccine & Gene Therapy Institute of FloridaJulien van Grevenynghe - Institut National de la Recherche ScientifiqueSaintedym Wills - ‡Department of Immunology and the Duke Human Vaccine Institute, Duke University, Durham, NC 27710;Lela Kardava - National Institute of Allergy and Infectious DiseasesBrian H. Santich - National Institute of Allergy and Infectious DiseasesClarisa M. Buckner - National Institute of Allergy and Infectious DiseasesRoshell Muir - Vaccine & Gene Therapy Institute of FloridaVirginie Tardif - Vaccine & Gene Therapy Institute of FloridaCarmen Nichols - Vaccine & Gene Therapy Institute of FloridaFrancesco Procopio - University Hospital of LausanneZhong He - Vaccine & Gene Therapy Institute of FloridaTalibah Metcalf - Vaccine & Gene Therapy Institute of FloridaKhader Ghneim - Vaccine & Gene Therapy Institute of FloridaMichela Locci - La Jolla Institute For Allergy & ImmunologyPetronella Ancuta - Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, CanadaJean-Pierre Routy - McGill University Health CentreLydie Trautmann - Vaccine & Gene Therapy Institute of FloridaYuxing Li - Scripps Research InstituteAdrian B. McDermott - Vaccine Research CenterRick A. Koup - Vaccine Research CenterConstantinos Petrovas - Vaccine Research CenterSteven A. Migueles - National Institute of Allergy and Infectious DiseasesMark Connors - National Institute of Allergy and Infectious DiseasesGeorgia D. Tomaras - ‡Department of Immunology and the Duke Human Vaccine Institute, Duke University, Durham, NC 27710;Susan Moir - National Institute of Allergy and Infectious DiseasesShane Crotty - University of California, San DiegoElias K. Haddad - Vaccine & Gene Therapy Institute of Florida
- Publication Details
- The Journal of immunology (1950), Vol.195(12), pp.5625-5636
- Publisher
- American Association of Immunologists
- Number of pages
- 12
- Grant note
- CTN 247 / Canadian Institutes of Health Research Canadian Trials Network/HIV Trial Network; Canadian Institutes of Health Research (CIHR) Center for AIDS Research Fonds de la Recherche en Sante du Quebec Maladies Infectieuses; Fonds de la Recherche en Sante du Quebec University of California, San Diego; University of California System AI064518 / Duke Center for AIDS Research Immunology Core (National Institutes of Health Grant) P30AI36214 / National Institute of Allergy and Infectious Diseases Development Grant 1RO1AI106482-01AI / National Institutes of Health Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 10867155-RKVA / American Foundation for AIDS Research R01AI102766 / National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant 103230 / Canadian Institutes of Health Research Grant; Canadian Institutes of Health Research (CIHR) P30AI064518 / 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)
- Identifiers
- 991019167757204721
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- Web of Science research areas
- Immunology