Transforming growth factor β induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Issue 5 (14th September 2005)

• Record Type: Journal Article
• Authors: Fantini, M C; Becker, C; Tubbe, I; Nikolaev, A; Lehr, H A; Galle, P; Neurath, M F
• Is Part Of: Gut. Volume 55:Issue 5(2006)
• Page Start: 671
• Page End: 680
• Publication Date: 2005-09-14
• Subjects: TGF-β, transforming growth factor β -- Tregs, regulatory T cells -- Ti-Tregs, TGF-β induced regulatory T cells -- IL, interleukin -- PBS, phosphate buffered saline -- TNF-α, tumour necrosis factor α -- IFN-γ, interferon γ -- RT-PCR, reverse transcription-polymerase chain reaction; transforming growth factor β -- FoxP3+ -- T cells -- experimental colitis; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2005.072801
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background and aims: The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+CD25+ regulatory T cells can be induced in the periphery from a population of CD25− T cells by treatment with transforming growth factor β (TGF-β). Here, we analysed the in vivo function of TGF-β induced regulatory T (Ti-Treg) cells in experimental colitis. Methods: Ti-Treg cells were generated in cell culture in the presence or absence of TGF-β and tested for their regulatory potential in experimental colitis using the CD4+CD62L+ T cell transfer model. Results: Ti-Treg cells significantly suppressed Th1 mediated colitis on CD4+CD62L+ T cell transfer in vivo, as shown by high resolution endoscopy, histology, immunohistochemistry, and cytokine analysis. Further analysis of in vivo and in vitro expanded Ti-Treg cells showed that exogenous interleukin 2 (IL-2) was crucial for survival and expansion of these cells. Conclusion: Our data suggest that regulatory Ti-Treg cells expand by TGF-β and exogenous IL-2 derived from effector T cells at the site of inflammation. In addition to Tr1 and thymic CD4+CD25+ T cells, peripheral Ti-Treg cells emerge as a class of regulatory T cells with therapeutic potential in T cell mediated chronic intestinal inflammation.