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The intestinal mucosa is suggested to support extrathymic T cell development, particularly for T cell receptor (TCR)-γδ intraepithelial lymphocytes (IELs). TCR-γδ cell development requires interleukin (IL)-7; IL-7−/− or IL-7 receptor−/− mice lack TCR-γδ 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-γδ IELs were restored, as were cryptopatches and Peyer's patches. TCR-γδ 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-γδ cells in situ within the intestinal epithelium and was crucial for organization of mucosal lymphoid tissue.

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