title: High IP-10 levels decrease T cell function in HIV-1-infected individuals on ART.
abstract: HIV-1-infected subjects, despite control of viral replication with ART, have an altered immune cytokine/chemokine milieu. Changes in systemic cytokines and chemokines can alter immune responses. IP-10, in particular, has been associated with pathogenesis in a number of conditions, and we found that IP-10 is increased in serum in subjects who are HIV-1 infected and on stable ART compared with HIV-1-uninfected individuals. In a series of in vitro studies, we found that PBMCs exposed to IP-10 showed a significant decrease in the number of cells capable of secreting IFN-γ, as well as other cytokines, when stimulated with recall antigens. Furthermore, treatment with IP-10 led to decreased antigen-specific calcium signaling and MAPK38 phosphorylation. Importantly, the cytokines, as well as proliferative responses, could be enhanced with an IP-10 Nab. Our findings suggest that IP-10-modulating drugs may potentially enhance T cell responses to vaccination and HIV-1 in HIV+ subjects on ART.
authors.affiliation: Department of Pathology and.
authors.forename: L A
authors.initials: LA
authors.lastname: Ramirez
authors.affiliation: Department of Pathology and.
authors.forename: T A
authors.initials: TA
authors.lastname: Arango
authors.affiliation: Department of Pathology and.
authors.forename: E
authors.initials: E
authors.lastname: Thompson
authors.affiliation: Department of Pathology and.
authors.forename: M
authors.initials: M
authors.lastname: Naji
authors.affiliation: AIDS Clinical Trials Unit, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: P
authors.initials: P
authors.lastname: Tebas
authors.affiliation: Department of Pathology and boyerj@mail.med.upenn.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Boyer
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D059425:Interferon-gamma Release Tests; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008875:Middle Aged; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054367:Receptors, CXCR3 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D000941:Antigens; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D006680:HLA Antigens; D054367:Receptors, CXCR3; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CXCL10; antiretroviral therapy; chemokines; immune responses; infection