Failures of these regulatory mechanisms contribute to the develop

Failures of these regulatory mechanisms contribute to the development of inflammatory bowel disease. In this study we demonstrate that the frequency of CD8+ Foxp3+ T cells is reduced in the peripheral blood of patients with ulcerative colitis. As these cells might play a currently underestimated role in the maintenance of intestinal homeostasis, we have investigated human and murine CD8+ Foxp3+ T cells generated by this website stimulating

naive CD8+ T cells in the presence of transforming growth factor-β and retinoic acid, mediators that are abundantly produced in the intestinal mucosa. These CD8+ Foxp3+ fully competent regulatory T cells show strong expression of regulatory molecules CD25, Gpr83 and CTLA-4 and exhibit cell–cell contact-dependent immunosuppressive activity in vitro. Our study illustrates a previously unappreciated critical role of CD8+ Foxp3+ T cells in controlling potentially dangerous T cells and in the maintenance of intestinal homeostasis. Regulatory T cells are believed to play a crucial role in the bowel’s adjustments to microbial antigens and in the modulation of tissue-damaging find more immune reactions; therefore, these cells are regarded as a promising

new therapeutic target.1 The most prominent population of regulatory T cells is the CD4+ subset. Various populations of thymically or peripherally induced regulatory T cells, such as CD4+ CD25+ T cells,2 CD4+ CD45RBlow T cells,3 type 1 regulatory T (Treg1) cells,4 and type 3 helper T (Th3) cells,5 have been L-gulonolactone oxidase described for the control of intestinal inflammation. However, less attention has been given to the inhibitory capability of CD8+ T cells, and, although several types of CD8+ regulatory T cells with various phenotypes seem to exist in humans and in experimental animals,6–11 the nature of the primary CD8+ regulatory T cells and the mechanisms underlying their generation remain elusive. Some populations of CD8+ regulatory T cells are believed

to be involved in the control of mucosal immune responses. An experimental model mimicking inflammatory bowel disease (IBD) uses the injection of CD4+ CD45RBhigh T cells into syngeneic mice deficient in the recombination activation gene 2 (Rag-2) to generate inflammation of the gut mucosa. In this model, Ménager-Marcq et al. demonstrated that CD8+ CD28− T cells, but not CD8+ CD28+ T cells, freshly isolated from the spleen or the gut efficiently prevent the development of colitis.12 In addition, Ho et al. identified a subset of CD8+ regulatory T cells characterized by CD8+ CD44−CD103high expression.13 Adoptive transfer of CD4+ T cells from mice that over-express tumour necrosis factor-α into immunodeficient Rag−/− mice induces ileitis, but co-transfer of CD8+ CD44−CD103+ T cells from wild-type mice attenuates the ileitis histology.

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