Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Clinical Investigation |
| Vol/bind | 119 |
| Udgave nummer | 8 |
| Sider (fra-til) | 2245-56 |
| Antal sider | 12 |
| ISSN | 0021-9738 |
| Status | Udgivet - 2009 |
Bibliografisk note
Keywords: CD8-Positive T-Lymphocytes; HLA-A2 Antigen; Heme Oxygenase-1; Humans; Immunophenotyping; Interferon-gamma; Interleukin-10; Lymphocyte Activation; Neoplasms; T-Lymphocytes, RegulatoryCitationsformater
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I: Journal of Clinical Investigation, Bind 119, Nr. 8, 2009, s. 2245-56.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Identification of heme oxygenase-1-specific regulatory CD8+ T cells in cancer patients
AU - Andersen, Mads Hald
AU - Sørensen, Rikke Baek
AU - Brimnes, Marie K
AU - Svane, Inge Marie
AU - Becker, Jürgen C
AU - thor Straten, Per
N1 - Keywords: CD8-Positive T-Lymphocytes; HLA-A2 Antigen; Heme Oxygenase-1; Humans; Immunophenotyping; Interferon-gamma; Interleukin-10; Lymphocyte Activation; Neoplasms; T-Lymphocytes, Regulatory
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 19662679
SN - 0021-9738
VL - 119
SP - 2245
EP - 2256
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 8
ER -