Control of CD8αα intestinal intraepithelial lymphocyte development by TGF-β

The molecular mechanisms directing the development of TCRαβ(+)CD8αα(+) intestinal intraepithelial lymphocytes (IEL) are not thoroughly understood. Here we show that transforming growth factor-β (TGF-β) controls the development of TCRαβ(+)CD8αα(+) IEL. Mice with either a TGF-β1 null mutation or a T cell-specific deletion of the TGF-β receptor I lacked TCRαβ(+)CD8αα(+) IEL, whereas transgenic mice that over-expressed TGF-β1 had an increased population of TCRαβ(+)CD8αα(+) IEL. Defective development of the TCRαβ(+)CD8αα(+) IEL thymic precursors (CD4(-)CD8(-)TCRαβ(+)CD5(+)) was observed in the absence of TGF-β. In addition, we showed that TGF-β signaling induced CD8α expression in TCRαβ(+)CD8αα(+) IEL thymic precursors and induced and maintained CD8α expression in peripheral populations of T cells. These data demonstrate a previously unrecognized role for TGF-β in the development of TCRαβ(+)CD8αα(+) IEL and the expression of CD8 in T cells.