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TGF-߱ production by CD4+CD25+ regulatory T cells is not essential for suppression of intestinal inflammation

Kullberg, M.C., Hay, V.H., Cheever, A.W., Mamura, M., Sher, A., Letterio, J.J., Shevach, E.M. and Piccirillo, C.A. (2005) TGF-߱ production by CD4+CD25+ regulatory T cells is not essential for suppression of intestinal inflammation. European Journal of Immunology, 35 (10). pp. 2886-2895. ISSN 0014-2980

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Naturally occurring CD4+CD25+ regulatory T cells (Treg) are potent suppressors of CD4+ and CD8+ T cell responses in vitro and inhibit several organ-specific autoimmune diseases. While most in vitro studies suggest that CD4+CD25+ Treg cells adopt a cytokine-independent but cell contact-dependent mode of T cell regulation, their precise mechanism of suppression in vivo remains largely unknown. Here we examine the functional contribution of Treg cell-derived TGF-1 and effector T cell responsiveness to TGF- in CD4+CD25+ T cell-mediated suppression of inflammatory bowel disease (IBD). We show that CD4+CD25+ Treg cells from either TGF-1+/+ or neonatal TGF-1-/- mice can suppress the incidence and severity of IBD as well as colonic IFN- mRNA expression induced by WT CD4+CD25- effector T cells. Furthermore, TGF--resistant Smad3-/- CD4+CD25+ Treg cells are equivalent to WT Treg cells in their capacity to suppress disease induced by either WT or Smad3-/- CD4+CD25- effector T cells. Finally, anti-TGF- treatment exacerbates the colitogenic potential of CD4+CD25- effector T cells in the absence of CD4+CD25+ Treg cells. Together, these data demonstrate that in certain situations CD4+CD25+ T cells are able to suppress intestinal inflammation by a mechanism not requiring Treg cell-derived TGF-1 or effector T cell/Treg cell responsiveness to TGF- via Smad3.

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Hull York Medical School (York)
Depositing User: York RAE Import
Date Deposited: 25 May 2009 14:45
Last Modified: 25 May 2009 14:45
Published Version: http://dx.doi.org/10.1002/eji.200526106
Status: Published
Publisher: John Wiley & Sons, Ltd
Identification Number: 10.1002/eji.200526106
URI: http://eprints.whiterose.ac.uk/id/eprint/6166

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