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Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals

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 a...

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Autores principales: Bharaj, Preeti, Chahar, Harendra Singh, Alozie, Ogechika K., Rodarte, Lizette, Bansal, Anju, Goepfert, Paul A., Dwivedi, Alok, Manjunath, N., Shankar, Premlata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184823/
https://www.ncbi.nlm.nih.gov/pubmed/25279955
http://dx.doi.org/10.1371/journal.pone.0109103
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author Bharaj, Preeti
Chahar, Harendra Singh
Alozie, Ogechika K.
Rodarte, Lizette
Bansal, Anju
Goepfert, Paul A.
Dwivedi, Alok
Manjunath, N.
Shankar, Premlata
author_facet Bharaj, Preeti
Chahar, Harendra Singh
Alozie, Ogechika K.
Rodarte, Lizette
Bansal, Anju
Goepfert, Paul A.
Dwivedi, Alok
Manjunath, N.
Shankar, Premlata
author_sort Bharaj, Preeti
collection PubMed
description 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.
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spelling pubmed-41848232014-10-07 Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals Bharaj, Preeti Chahar, Harendra Singh Alozie, Ogechika K. Rodarte, Lizette Bansal, Anju Goepfert, Paul A. Dwivedi, Alok Manjunath, N. Shankar, Premlata PLoS One Research Article 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. Public Library of Science 2014-10-03 /pmc/articles/PMC4184823/ /pubmed/25279955 http://dx.doi.org/10.1371/journal.pone.0109103 Text en © 2014 Bharaj et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bharaj, Preeti
Chahar, Harendra Singh
Alozie, Ogechika K.
Rodarte, Lizette
Bansal, Anju
Goepfert, Paul A.
Dwivedi, Alok
Manjunath, N.
Shankar, Premlata
Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
title Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
title_full Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
title_fullStr Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
title_full_unstemmed Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
title_short Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals
title_sort characterization of programmed death-1 homologue-1 (pd-1h) expression and function in normal and hiv infected individuals
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184823/
https://www.ncbi.nlm.nih.gov/pubmed/25279955
http://dx.doi.org/10.1371/journal.pone.0109103
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