期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 35, 期 10, 页码 2886-2895出版社
WILEY
DOI: 10.1002/eji.200526106
关键词
CD4(+) regulatory T cells; TGF-beta; autoimmunity; suppression
类别
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-beta 1 and effector T cell responsiveness to TGF-beta in CD4(+)CD25(+) T cell-mediated suppression of inflammatory bowel disease (IBD). We show that CD4(+)CD25(+) Treg cells from either TGF-beta 1(+/+) or neonatal TGF-beta 1(-/-) mice can suppress the incidence and severity of IBD as well as colonic IFN-gamma mRNA expression induced by WT CD4(+)CD25(-) effector T cells. Furthermore, TGF-beta-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-beta 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-beta 1 or effector T cell/Treg cell responsiveness to TGF-beta via Smad3.
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