Generation and function of immunosuppressive human and murine CD8+ T cells by transforming growth factor-β and retinoic acid
| Autor: | Fleissner, Diana, Frede, Annika, Knott, Markus, Knuschke, Torben, Geffers, Robert, Hansen, Wiebke, Dobos, Gustav, Langhorst, Jost, Buer, Jan, Westendorf, Astrid |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Cytotoxicity Immunologic Male Pore Forming Cytotoxic Proteins Green Fluorescent Proteins Medizin Gene Expression Cell Count Mice Transgenic Tretinoin Cell Communication CD8-Positive T-Lymphocytes Lymphocyte Activation Granzymes Immunophenotyping Interferon-gamma Mice Antigens CD T-Lymphocyte Subsets Transforming Growth Factor beta Immune Tolerance Animals Humans CTLA-4 Antigen Aged Cell Proliferation Aged 80 and over Mice Knockout Mice Inbred BALB C Interleukin-2 Receptor alpha Subunit Forkhead Transcription Factors Original Articles Dendritic Cells Middle Aged Coculture Techniques Mice Inbred C57BL Leukocytes Mononuclear Colitis Ulcerative Female |
| Popis: | The intestinal immune system is constantly challenged by foreign antigens and commensal bacteria. Therefore, proper control of the intestinal microenvironment is required. One important arm of this regulatory network consists of regulatory T cells. In contrast to CD4(+) Foxp3(+) regulatory T cells, which have been well characterized, immunomodulatory CD8(+) T cells that express Foxp3 are less well defined in terms of their generation and function. 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 stimulating naive CD8(+) T cells in the presence of transforming growth factor-beta 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. |
| Databáze: | OpenAIRE |
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