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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.
- 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.
- Subjects :
- Animals
Cell Proliferation
Colitis immunology
Cytokines immunology
Immunohistochemistry
L-Selectin immunology
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, SCID
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes, Regulatory immunology
Th1 Cells immunology
Adoptive Transfer methods
CD4-Positive T-Lymphocytes immunology
Colitis therapy
Forkhead Transcription Factors immunology
Transforming Growth Factor beta immunology
Subjects
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