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SHR Neuro Cancer Cardio Lipid Metab Microb

Andersen, MH; Sorensen, RB; Brimnes, MK; Svane, IM; Becker, JC; Straten, PT.
Identification of heme oxygenase-1-specific regulatory CD8+ T cells in cancer patients.
J Clin Invest. 2009; 119(8):2245-2256 Doi: 10.1172/JCI38739 [OPEN ACCESS]
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Co-authors Med Uni Graz: Becker Jürgen Christian
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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.
Find related publications in this database (using NLM MeSH Indexing): CD8-Positive T-Lymphocytes - immunology; HLA-A2 Antigen - immunology; Heme Oxygenase-1 - immunology; Humans -; Immunophenotyping -; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Lymphocyte Activation -; Neoplasms - immunology; T-Lymphocytes, Regulatory - immunology