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T Regulatory Cells Maintain Intestinal Homeostasis by Suppressing γδ T Cells
Park, Sung-Gyoo,Mathur, Ramkumar,Long, Meixiao,Hosh, Namiko,Hao, Liming,Hayden, Matthew S.,Ghosh, Sankar Elsevier 2010 Immunity Vol.33 No.5
<P><B>Summary</B></P><P>Immune tolerance against enteric commensal bacteria is important for preventing intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1 (<I>Pdk1</I>) in T cells via <I>Cd4-Cre</I> induced chronic inflammation of the intestine despite the importance of PDK1 in T cell activation. Analysis of colonic intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased CD8α<SUP>+</SUP> T cell receptor (TCR)γδ<SUP>+</SUP> T cells, including an interleukin-17 (IL-17)-expressing population. TCRγδ<SUP>+</SUP> T cells were responsible for the inflammatory colitis as shown by the fact that deletion of <I>Tcrd</I> abolished spontaneous colitis in the PDK1-deficient mice. This dysregulation of intestinal TCRγδ<SUP>+</SUP> T cells was attributable to a reduction in the number and functional capacity of PDK1-deficient T regulatory (Treg) cells. Adoptive transfer of wild-type Treg cells abrogated the spontaneous activation and proliferation of intestinal TCRγδ<SUP>+</SUP> T cells observed in PDK1-deficient mice and prevented the development of colitis. Therefore, suppression of intestinal TCRγδ<SUP>+</SUP> T cells by Treg cells maintains enteric immune tolerance.</P> <P><B>Highlights</B></P><P>► PDK1 is essential for Treg cell function including suppression and IL-10 production ► γδ T cells can cause colitis, even in the absence of functional αβ T cells ► γδ T cell-mediated colitis depends on the presence of commensal bacteria ► Treg cells can directly suppress γδ T cells through the production of IL-10</P>