Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.

Détails

ID Serval
serval:BIB_8DF366DBE66A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.
Périodique
Journal of Immunology
Auteur(s)
Cubas R., van Grevenynghe J., Wills S., Kardava L., Santich B.H., Buckner C.M., Muir R., Tardif V., Nichols C., Procopio F., He Z., Metcalf T., Ghneim K., Locci M., Ancuta P., Routy J.P., Trautmann L., Li Y., McDermott A.B., Koup R.A., Petrovas C., Migueles S.A., Connors M., Tomaras G.D., Moir S., Crotty S., Haddad E.K.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
195
Numéro
12
Pages
5625-5636
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Adult, Antibodies, Viral/immunology, Antibody Formation, B-Lymphocytes/immunology, B-Lymphocytes/virology, Cell Differentiation, Cells, Cultured, Cellular Reprogramming, Chronic Disease, HIV, HIV Infections/immunology, Humans, Immunologic Memory, Interleukin-2/immunology, Middle Aged, Signal Transduction, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/virology, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/01/2016 18:30
Dernière modification de la notice
08/05/2019 21:50
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