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

Gut. 2006 May;55(5):671-80. doi: 10.1136/gut.2005.072801. Epub 2005 Sep 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Colitis / immunology
  • Colitis / therapy*
  • Cytokines / immunology
  • Forkhead Transcription Factors / 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
  • Transforming Growth Factor beta / immunology*


  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Transforming Growth Factor beta
  • L-Selectin