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

Adriano Boasso, Andrew W. Hardy, Alan L. Landay, Jeffrey L. Martinson, Stephanie A. Anderson, Matthew J. Dolan, Mario Clerici, Gene M. Shearer

Research output: Contribution to journalArticle


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)-α, but not IFN-γ, production. Inhibition of endocytosis, required for HIV-induced IFN-α production, prevented PDL-1 upregulation. IFN-α-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-α-dependent. IFN-α-receptor subunit 2 (IFNAR2), was expressed only by CCR5+ T cells and monocytes, explaining why these leukocytes responded to HIV-induced IFN-α. Finally, T cell proliferation was improved by PDL-1 blockade in HIV-treated PBMC. In the setting of HIV infection, IFN-α may negatively affect T cell responses by inducing PDL-1.

Original languageEnglish
Pages (from-to)132-144
Number of pages13
JournalClinical Immunology
Issue number1
Publication statusPublished - Oct 2008



  • Antigen-presenting cells
  • CCR5
  • HIV-1
  • IFN-α
  • Monocytes
  • PDL-1
  • Plasmacytoid dendritic cells
  • Proliferation
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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