Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals

PLoS One. 2014 Oct 3;9(10):e109103. doi: 10.1371/journal.pone.0109103. eCollection 2014.

Abstract

Chronic immune activation that persists despite anti-retroviral therapy (ART) is the strongest predictor of disease progression in HIV infection. Monocyte/macrophages in HIV-infected individuals are known to spontaneously secrete cytokines, although neither the mechanism nor the molecules involved are known. Here we show that overexpression of the newly described co-stimulatory molecule, PD1 homologue (PD-1H) in human monocyte/macrophages is sufficient to induce spontaneous secretion of multiple cytokines. The process requires signaling via PD-1H as cytokine secretion could be abrogated by deletion of the cytoplasmic domain. Such overexpression of PD-1H, associated with spontaneous cytokine expression is seen in monocytes from chronically HIV-infected individuals and this correlates with immune activation and CD4 depletion, but not viral load. Moreover, antigen presentation by PD-1H-overexpressing monocytes results in enhanced cytokine secretion by HIV-specific T cells. These results suggest that PD-1H might play a crucial role in modulating immune activation and immune response in HIV infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B7 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Viral Load / immunology

Substances

  • B7 Antigens
  • Cytokines
  • VSIR protein, human