作者
Rafael A Cubas, Joseph C Mudd, Anne-Laure Savoye, Matthieu Perreau, Julien Van Grevenynghe, Talibah Metcalf, Elizabeth Connick, Amie Meditz, Gordon J Freeman, Guillermo Abesada-Terk Jr, Jeffrey M Jacobson, Ari D Brooks, Shane Crotty, Jacob D Estes, Giuseppe Pantaleo, Michael M Lederman, Elias K Haddad
发表日期
2013/4
期刊
Nature medicine
卷号
19
期号
4
页码范围
494-499
出版商
Nature Publishing Group US
简介
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 …
学术搜索中的文章
RA Cubas, JC Mudd, AL Savoye, M Perreau… - Nature medicine, 2013