title: Acute HIV-1 infection is associated with increased plasma levels of heme oxygenase-1 and presence of heme oxygenase-1-specific regulatory T cells.
abstract: Heme oxygenase-1 (HO-1) is an inducible stress response protein with potent anti-inflammatory activity and recent data suggest a potentially beneficial role in HIV pathogenesis. We investigated the impact of HO-1 and a novel subset of HO-1-specific CD8 regulatory T cells on virus-specific T-cell immunity in HIV-1-infected individuals.
  
  
  
  HO-1 protein levels were quantified in plasma from individuals at different stages of HIV-1 disease and longitudinally following primary HIV infection. HO-1-specific CD8 T cells were investigated by flow cytometry using human leukocyte antigen (HLA) class I pentamers. Flow-sorted HO-1-specific CD8 T cells were cultured and tested for suppressive activity on HIV-1-specific cytotoxic T-cell clones clones. HO-1 gene expression was determined in sorted peripheral blood mononuclear cell (PBMC) subsets from individuals with acute HIV-1 infection.
  
  
  
  HO-1 plasma levels were significantly increased in HIV-1 infection, with the highest levels in individuals with acute HIV-1 infection, and gradually declined over time. The frequency of CD8 T cells specific for HO-1 was elevated in study participants with primary HIV-1 infection and flow-sorted HO-1-specific CD8 T cells were capable of suppressing HIV-1-specific lysis of cytotoxic T-cell clones clones. HO-1 gene expression was upregulated in multiple immune cell subsets during acute HIV-1 infection and HO-1 overexpression modulated anti-HIV immunity in vitro.
  
  
  
  Our data suggest that HO-1 is induced during acute HIV-1 infection, likely mediating anti-inflammatory effects and driving expansion of HO-1-specific CD8 regulatory T cells capable of suppressing HIV-1-specific immune responses in vitro. The investigation of HO-1 and the novel CD8 regulatory cell type described here provide further insight into immune regulation in HIV-1 infection and may hold potential for future immunotherapeutic intervention.
authors.affiliation: aRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA bUniversity of Münster, Münster, North Rhine-Westphalia cDepartment of Viral Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany dDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA eI. Department of Medicine, University Medical Center Hamburg-Eppendorf fGerman Center for Infection Research (DZIF), Standort Hamburg-Lüebeck-Borstel, Hamburg, Germany.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Angin
authors.forename: Anahita
authors.initials: A
authors.lastname: Fathi
authors.forename: Melanie
authors.initials: M
authors.lastname: King
authors.forename: Mary B
authors.initials: MB
authors.lastname: Ledoux
authors.forename: Alicja
authors.initials: A
authors.lastname: Piechocka-Trocha
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Marylyn M
authors.initials: MM
authors.lastname: Addo
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D016130:Immunophenotyping; D008137:Longitudinal Studies; D010949:Plasma / Q000201:enzymology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051547:Heme Oxygenase-1