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

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 β (TGF-β). Here, we analysed the in vivo function of TGF-β 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-β 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-β 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.

  • TGF-β, transforming growth factor β
  • Tregs, regulatory T cells
  • Ti-Tregs, TGF-β induced regulatory T cells
  • IL, interleukin
  • PBS, phosphate buffered saline
  • TNF-α, tumour necrosis factor α
  • IFN-γ, interferon γ
  • RT-PCR, reverse transcription-polymerase chain reaction
  • transforming growth factor β
  • FoxP3+
  • T cells
  • experimental colitis
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