@article{38af7d77d57a490daa909f46d139e86d,
title = "Programmed death-1-induced interleukin-10 production by monocytes impairs CD4 + T cell activation during HIV infection",
abstract = "Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4 + T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4 + T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.",
author = "Said, {Elias A.} and Dupuy, {Franck P.} and Lydie Trautmann and Yuwei Zhang and Yu Shi and Mohamed El-Far and Hill, {Brenna J.} and Alessandra Noto and Petronela Ancuta and Yoav Peretz and Fonseca, {Simone G.} and {Van Grevenynghe}, Julien and Boulassel, {Mohamed R.} and Julie Bruneau and Shoukry, {Naglaa H.} and Routy, {Jean Pierre} and Douek, {Daniel C.} and Haddad, {Elias K.} and Sekaly, {Rafick Pierre}",
note = "Funding Information: We thank the subjects for their participation in this study. We also thank M. Legault and C. Grignon for their clinical assistance with the recruitment of study subjects. We are grateful to V.A. Evans and J.D. Schatzle for help in manuscript revision. E.A.S., L.T., M.E.-F. and J.V.G. are funded by the Canadian Institutes of Health Research (CIHR). N.H.S. holds a joint New Investigator Award from the Canadian Foundation for Infectious Diseases and CIHR. J.B. and J.-P.R. are clinician-scientists supported by Fonds de la recherche en sant{\'e} du Qu{\'e}bec. R.-P.S. is the Canada Research Chair in Human Immunology. This study was supported by funds from the US National Institutes of Health, the CIHR, the Canadian Foundation for AIDS Research, the Fonds de la recherche en sant{\'e} du Qu{\'e}bec AIDS and Infectious Disease Network (SIDA-MI) and the Canadian Network for Vaccines and Immunotherapeutics. This study was funded in part by the Intramural Program of the US National Institutes of Health.Vectors were generously provided by E. Cohen at the Institut de Recherches Cliniques de Montr{\'e}al. The lentiviral vector pWPI (empty vector), packaging plasmid psPAX2 and envelope plasmid pMD2G were generously provided by D. Trono (University of Geneva).",
year = "2010",
month = apr,
doi = "10.1038/nm.2106",
language = "English",
volume = "16",
pages = "452--459",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "4",
}
