title: Identification of heme oxygenase-1-specific  regulatory CD8+ T cells in cancer patients.
abstract: Treg deficiencies are associated with autoimmunity. Conversely, CD4+ and CD8+ Tregs accumulate in the tumor microenvironment and are associated with prevention of antitumor immunity and anticancer immunotherapy. Recently, CD4+ Tregs have been much studied, but little is known about CD8+ Tregs and the antigens they recognize. Here, we describe what we believe to be the first natural target for CD8+ Tregs. Naturally occurring HLA-A2-restricted CD8+ T cells specific for the antiinflammatory molecule heme oxygenase-1 (HO-1) were able to suppress cellular immune responses with outstanding efficacy. HO-1-specific CD8+ T cells were detected ex vivo and in situ among T cells from cancer patients. HO-1-specific T cells isolated from the peripheral blood of cancer patients inhibited cytokine release, proliferation, and cytotoxicity of other immune cells. Notably, the inhibitory effect of HO-1-specific T cells was far more pronounced than that of conventional CD4+CD25+CD127- Tregs. The inhibitory activity of HO-1-specific T cells seemed at least partly to be mediated by soluble factors. Our data link the cellular stress response to the regulation of adaptive immunity, expand the role of HO-1 in T cell-mediated immunoregulation, and establish a role for peptide-specific CD8+ T cells in regulating cellular immune responses. Identification of potent antigen-specific CD8+ Tregs may open new avenues for therapeutic interventions in both autoimmune diseases and cancer.
authors: Center for Cancer Immune Therapy, Department of Hematology, Herlev University Hospital, Herlev, Denmark. mahaan01@heh.regionh.dk
authors: Mads Hald
authors: MH
authors: Andersen
authors: Rikke Baek
authors: RB
authors: Sørensen
authors: Marie K
authors: MK
authors: Brimnes
authors: Inge Marie
authors: IM
authors: Svane
authors: Jürgen C
authors: JC
authors: Becker
authors: Per
authors: P
authors: thor Straten
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D051547:Heme Oxygenase-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen; D016753:Interleukin-10; D007371:Interferon-gamma; D051547:Heme Oxygenase-1