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

The molecular mechanisms that direct the development of TCRαβ⁺ CD8αα⁺ intestinal intraepithelial lymphocytes (IELs) are not thoroughly understood. Here we show that transforming growth factor-β 2 (TGF-β 2) controls the development of TCRβ αβ⁺ CD8β αβ α⁺ IELs. Mice with either a null mutation in the gene encoding TGF-β 21 or T cell-specific deletion of TGF-β receptor I lacked TCRβ αβ⁺ CD8β αβ α⁺ IELs, whereas mice with transgenic overexpression of TGF-β 21 had a larger population of TCRβ αβ⁺ CD8β αβ α⁺ IELs. We observed defective development of the TCRβ αβ⁺ CD8β αβ α⁺ IEL thymic precursors (CD4 -CD8 -TCRβ αβ⁺ CD5⁺) in the absence of TGF-β 2. In addition, we found that TGF-β 2 signaling induced CD8β α expression in TCRβ αβ⁺ CD8β αβ α⁺ IEL thymic precursors and induced and maintained CD8β ± expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-β 2 in the development of TCRβ αβ⁺ CD8β αβ ⁺IELs and the expression of CD8β α in T cells.