[HTML][HTML] Identification of heme oxygenase-1–specific regulatory CD8+ T cells in cancer patients

MH Andersen, RB Sørensen… - The Journal of …, 2009 - Am Soc Clin Investig
MH Andersen, RB Sørensen, MK Brimnes, IM Svane, JC Becker, P thor Straten
The Journal of clinical investigation, 2009Am Soc Clin Investig
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) …
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.
The Journal of Clinical Investigation