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


CONCLUSIONS
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.
Fantini
M C
MC
Laboratory of Immunology, I Medical Clinic, Johannes Gutenberg University of Mainz, Mainz, Germany.
Becker
C
C
Tubbe
I
I
Nikolaev
A
A
Lehr
H A
HA
Galle
P
P
Neurath
M F
MF
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology*; D007150:Immunohistochemistry; D019041:L-Selectin / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta; D019041:L-Selectin