Enterocyte expression of interleukin 7 induces development of γδ T cells and Peyer's patches

The intestinal mucosa is suggested to support extrathymic T cell development, particularly for T cell receptor (TCR)-gamma delta intraepithelial lymphocytes (IELs). TCR-gamma delta cell development requires interleukin (IL)-7; IL-7(-/-) or IL-7 receptor(-/-) mice lack TCR-gamma delta cells. Using the intestinal fatty acid binding protein (iFABP) promoter, we reinstated expression of IL-7 to mature enterocytes of IL-7(-/-) mice (iFABP-IL7). In iFABP-IL7 mice, TCR-gamma delta IELs were restored, as were cryptopatches and Peyer's patches. TCR-gamma delta cells remained absent from all other tissues. Likewise, T cell development in thymus and B cell maturation in the bone marrow and spleen retained the IL-7(-/-) phenotype. Thus, IL-7 expression by enterocytes was sufficient for extrathymic development of TCR-gamma delta cells in situ within the intestinal epithelium and was crucial for organization of mucosal lymphoid tissue.