Inadequate T follicular cell help impairs B cell immunity during HIV infection.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_F10C91F4362C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inadequate T follicular cell help impairs B cell immunity during HIV infection.
Périodique
Nature Medicine
Auteur(s)
Cubas R.A., Mudd J.C., Savoye A.L., Perreau M., van Grevenynghe J., Metcalf T., Connick E., Meditz A., Freeman G.J., Abesada-Terk G., Jacobson J.M., Brooks A.D., Crotty S., Estes J.D., Pantaleo G., Lederman M.M., Haddad E.K.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
19
Numéro
4
Pages
494-499
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations. We report here that even though there is an expansion of follicular helper T (TFH) 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 TFH cell function. In fact, we show that engagement of PD-1 on TFH 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 TFH cell-mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on TFH cells. These results demonstrate a role for TFH 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.
Pubmed
Web of science
Création de la notice
08/04/2013 15:48
Dernière modification de la notice
03/03/2018 22:37
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