title: Immune Activation at Sites of HIV/TB Co-Infection Contributes to the Pathogenesis of HIV-1 Disease.
abstract: Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed. The T cell phenotype and activation status of HIV-1 p24 + T cells in PFMC and PBMC from HIV/TB patients were determined. We found that T cell and macrophage-specific and non-specific soluble markers of immune activation, sCD27, sCD163, IL1Ra, and sCD14, were higher in pleural fluid as compared to plasma from HIV/TB co-infected subjects, and higher as compared to pleural fluid from TB mono-infected subjects. Intestinal fatty acid-binding protein, a marker of intestinal tract damage, in plasma from HIV/TB co-infected patients was not different than that in HIV+ subjects. Expression of HLADR and CD38 double positive (HLADR/CD38) on CD4 T cells, and CD69+ on CD8 T cells correlated with pleural fluid viral load, and inversely with blood CD4 T cell count. Higher expression of HLADR/CD38 and CCR5 on CD4 T cells, and HLADR/CD38 and CD69 on CD8 T cells in PFMC were limited to effector memory populations. HIV-1 p24+ CD8 negative (includes CD4 + and double negative T cells) effector memory T cells in PFMC had higher expression of HLADR/CD38, Ki67, and CCR5 compared to HIV-1 p24- CD8 negative PFMC. Cumulatively, these data indicate that sites of HIV/TB co-infection are the source of intense immune activation.
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Qinglai
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Ismail
authors.initials: I
authors.lastname: Sayin
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, Ohio, United States of America.|Veterans Affairs Medical Center, Cleveland, Ohio, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.affiliation: Department of Medicine, Makerere University, Kampala, Uganda.|Division of Infectious Disease, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Joint Clinical Research Center, Kampala, Uganda.
authors.forename: Joy
authors.initials: J
authors.lastname: Baseke
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, Ohio, United States of America.|Veterans Affairs Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D060085:Coinfection / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens