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Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis.

Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis.

Authors :
Fantini MC
Becker C
Tubbe I
Nikolaev A
Lehr HA
Galle P
Neurath MF
Source :
Gut [Gut] 2006 May; Vol. 55 (5), pp. 671-80. Date of Electronic Publication: 2005 Sep 14.
Publication Year :
2006

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 beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta induced regulatory T (Ti-Treg) cells in experimental colitis.<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
0017-5749
Volume :
55
Issue :
5
Database :
MEDLINE
Journal :
Gut
Publication Type :
Academic Journal
Accession number :
16162681
Full Text :
https://doi.org/10.1136/gut.2005.072801