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 beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta 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-beta 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-beta 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.
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 beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta 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-beta 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-beta 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.
Authors: Catherine Van Montfrans; Maria Sol Rodriguez Pena; Inge Pronk; Fiebo J W Ten Kate; Anje A Te Velde; Sander J H Van Deventer Journal: Gastroenterology Date: 2002-12 Impact factor: 22.682
Authors: Catherine Van Montfrans; Erik Hooijberg; Maria Sol Rodriguez Pena; Esther C De Jong; Hergen Spits; Anje A Te Velde; Sander J H Van Deventer Journal: Gastroenterology Date: 2002-12 Impact factor: 22.682
Authors: M F Neurath; B Weigmann; S Finotto; J Glickman; E Nieuwenhuis; H Iijima; A Mizoguchi; E Mizoguchi; J Mudter; P R Galle; A Bhan; F Autschbach; B M Sullivan; S J Szabo; L H Glimcher; R S Blumberg Journal: J Exp Med Date: 2002-05-06 Impact factor: 14.307
Authors: J Grundström; L Linton; S Thunberg; H Forsslund; I Janczewska; R Befrits; M van Hage; G Gafvelin; M Eberhardson Journal: Clin Exp Immunol Date: 2012-08 Impact factor: 4.330
Authors: Christian Becker; Sabine Stoll; Tobias Bopp; Edgar Schmitt; Helmut Jonuleit Journal: Med Microbiol Immunol Date: 2006-05-20 Impact factor: 3.402