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

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19 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 1 2014
Externally publishedYes

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ASJC Scopus subject areas

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

Cite this

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