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

Preeti Bharaj, Harendra Singh Chahar, Ogechika K. Alozie, Lizette Rodarte, Anju Bansal, Paul A. Goepfert, Alok Dwivedi, N. Manjunath, Premlata Shankar

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Article numbere109103
JournalPloS one
Volume9
Issue number10
DOIs
StatePublished - Oct 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Bharaj, P., Chahar, H. S., Alozie, O. K., Rodarte, L., Bansal, A., Goepfert, P. A., Dwivedi, A., Manjunath, N., & Shankar, P. (2014). Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals. PloS one, 9(10), [e109103]. https://doi.org/10.1371/journal.pone.0109103