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

Academic Article

Abstract

  • Chronic immune activation that persists despite antiretroviral 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.
  • Published In

  • PLoS One  Journal
  • Digital Object Identifier (doi)

    Author List

  • Bharaj P; Chahar HS; Alozie OK; Rodarte L; Bansal A; Goepfert PA; Dwivedi A; Manjunath N; Shankar P
  • Volume

  • 9
  • Issue

  • 10