PDL-1 upregulation on monocytes and T cells by HIV via type I interferon: restricted expression of type I interferon receptor by CCR5-expressing leukocytes.
The programmed death (PD)-1 interacts with its ligand (PDL-1) delivering a negative signal to T cells. During human immunodeficiency virus (HIV)-1 infection PD-1 and PDL-1 expressions are increased. Here we show that monocytes and CCR5(+) T cells of HIV-uninfected donors upregulated PDL-1 upon in vitro exposure to HIV. HIV-induced PDL-1 required interferon (IFN)-alpha, but not IFN-gamma, production. Inhibition of endocytosis, required for HIV-induced IFN-alpha production, prevented PDL-1 upregulation. IFN-alpha-inducing Toll-like receptor (TLR) agonists increased PDL-1 on monocytes and CCR5(+) T cells. CD80 and CD86 were also increased on monocytes and CCR5(+) T cells after HIV exposure, but only CD80 was IFN-alpha-dependent. IFN-alpha-receptor subunit 2 (IFNAR2), was expressed only by CCR5(+) T cells and monocytes, explaining why these leukocytes responded to HIV-induced IFN-alpha. Finally, T cell proliferation was improved by PDL-1 blockade in HIV-treated PBMC. In the setting of HIV infection, IFN-alpha may negatively affect T cell responses by inducing PDL-1.
Boasso
Adriano
A
Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. a.boasso@imperial.ac.uk
Hardy
Andrew W
AW
Landay
Alan L
AL
Martinson
Jeffrey L
JL
Anderson
Stephanie A
SA
Dolan
Matthew J
MJ
Clerici
Mario
M
Shearer
Gene M
GM
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D023241:Antiretroviral Therapy, Highly Active; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000276:immunology / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D019562:Viral Load
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C508033:IFNAR2 protein, human; D007370:Interferon Type I; D019713:Receptors, CCR5; D051193:Toll-Like Receptors; D053633:Receptor, Interferon alpha-beta