Control of the development of CD8??+ intestinal intraepithelial lymphocytes by TGF-?.

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

SUBMITTER: Konkel JE 

PROVIDER: S-EPMC3062738 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature