@article{9cc5dc10834c11df928f000ea68e967b,
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.",
author = "Andersen, {Mads Hald} and S{\o}rensen, {Rikke Baek} and Brimnes, {Marie K} and Svane, {Inge Marie} and Becker, {J{\"u}rgen C} and {thor Straten}, Per",
note = "Keywords: CD8-Positive T-Lymphocytes; HLA-A2 Antigen; Heme Oxygenase-1; Humans; Immunophenotyping; Interferon-gamma; Interleukin-10; Lymphocyte Activation; Neoplasms; T-Lymphocytes, Regulatory",
year = "2009",
language = "English",
volume = "119",
pages = "2245--56",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "8",
}
