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

52 Citations (Scopus)

Abstract

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
Volume129
Issue number1
DOIs
Publication statusPublished - Oct 2008

Fingerprint

Interferon alpha-beta Receptor
Interferon Type I
Monocytes
Interferons
Leukocytes
Up-Regulation
HIV
T-Lymphocytes
Virus Diseases
Interferon Receptors
Toll-Like Receptors
Endocytosis
HIV-1
Cell Proliferation
Ligands

Keywords

  • 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

Cite this

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

In: Clinical Immunology, Vol. 129, No. 1, 10.2008, p. 132-144.

Research output: Contribution to journalArticle

Boasso, Adriano ; Hardy, Andrew W. ; Landay, Alan L. ; Martinson, Jeffrey L. ; Anderson, Stephanie A. ; Dolan, Matthew J. ; Clerici, Mario ; Shearer, Gene M. / 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. In: Clinical Immunology. 2008 ; Vol. 129, No. 1. pp. 132-144.
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