title: Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals.
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.
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: Preeti
authors.initials: P
authors.lastname: Bharaj
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: Harendra Singh
authors.initials: HS
authors.lastname: Chahar
authors.affiliation: Department of Internal Medicine, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: Ogechika K
authors.initials: OK
authors.lastname: Alozie
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: Lizette
authors.initials: L
authors.lastname: Rodarte
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Biomedical Sciences, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: Alok
authors.initials: A
authors.lastname: Dwivedi
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
authors.affiliation: Center of Excellence for Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, United States of America.
authors.forename: Premlata
authors.initials: P
authors.lastname: Shankar
mesh_terms: D060887:B7 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D019562:Viral Load / Q000276:immunology
chemical_list: D060887:B7 Antigens; D016207:Cytokines; C000588758:VSIR protein, human