title: Mycobacterium tuberculosis recall antigens suppress HIV-1 replication in anergic donor cells via CD8+ T cell expansion and increased IL-10 levels.
abstract: Mycobacterium tuberculosis (MTb) is the leading cause of death in the setting of AIDS. MTb enhances the pathogenicity and accelerates the course of HIV disease and, furthermore, infection with HIV-1 increases the risk of reactivation or reinfection with MTb. In this study, we show that host-specific recall responses to one pathogen, MTb, has a direct effect upon the regulation of a second pathogen, HIV-1. Using cells from immunocompetent former tuberculosis (TB) patients who displayed either a persistently positive (responsive) or negative (anergic), delayed-type hypersensitivity (DTH) reaction to intradermal injection of purified protein derivative (PPD), we investigated the effect of recall Ags to MTb upon the replication of HIV-1 primary isolates in vitro. We show that HIV-1 replication of a T cell-tropic isolate was significantly impaired in MTb-stimulated PBMC from PPD-anergic donors. Furthermore, these donors displayed a significant increase in CD8(+) T cells and IL-10 levels and lower levels of IL-2 and TNF-alpha relative to PPD-responsive donors in response to PPD stimulation. Strikingly, CD8(+) T cell depletion and blocking of IL-10 significantly increased HIV-1 replication in these PPD-anergic donors, indicating that an immunosuppressive response to MTb recall Ags inhibits HIV-1 replication in PPD-anergic individuals. Therefore, immunotherapeutic approaches aimed at recapitulating Ag-specific MTb anergy in vivo could result in novel and effective approaches to inhibit HIV-1 disease progression in MTb/HIV-1 coinfection.
authors.affiliation: Center for Blood Research and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Ranjbar
authors.forename: Nary
authors.initials: N
authors.lastname: Ly
authors.forename: Sok
authors.initials: S
authors.lastname: Thim
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reynes
authors.forename: Anne E
authors.initials: AE
authors.lastname: Goldfeld
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy; D016207:Cytokines / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000276:immunology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D000942:Antigens, Bacterial; D016207:Cytokines; D007166:Immunosuppressive Agents; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10