Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β

The molecular mechanisms that direct the development of TCR alpha beta(+)CD8 alpha alpha(+) intestinal intraepithelial lymphocytes (IELs) are not thoroughly understood. Here we show that transforming growth factor-beta (TGF-beta) controls the development of TCR alpha beta(+)CD8 alpha alpha(+) IELs. Mice with either a null mutation in the gene encoding TGF-beta 1 or T cell-specific deletion of TGF-beta receptor I lacked TCR alpha beta(+)CD8 alpha alpha(+) IELs, whereas mice with transgenic overexpression of TGF-beta 1 had a larger population of TCR alpha beta(+)CD8 alpha alpha(+) IELs. We observed defective development of the TCR alpha beta(+)CD8 alpha alpha(+) IEL thymic precursors (CD4(-)CD8(-)TCR alpha beta(+)CD5(+)) in the absence of TGF-beta. In addition, we found that TGF-beta signaling induced CD8 alpha expression in TCR alpha beta(+)CD8 alpha alpha(+) IEL thymic precursors and induced and maintained CD8 alpha expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-beta in the development of TCR alpha beta(+)CD8 alpha alpha(+) IELs and the expression of CD8 alpha in T cells.