The Role of IL-7 in Thymic and Extrathymic Development of TCRγδ Cells

IL-7-deficient (IL-7−/−) mice have reduced numbers of B and TCRαβ cells, but lack mature TCRγδ cells. Although most T cell development occurs in the thymus, some intestinal intraepithelial lymphocytes (IEL), including TCRγδ cells, can develop extrathymically. Epithelial cells in both thymus and intestine synthesize IL-7, suggesting that TCRγδ cell development could occur in either site. To evaluate the role of thymic IL-7 in development of TCRγδ cells, newborn TCRβ-deficient (TCRβ−/−) thymi were grafted to IL-7−/− mice. Donor- and host-derived TCRγδ cells were recovered from thymus grafts, spleen, and IEL. However, when IL-7−/− thymi were grafted to TCRβ−/− mice, no development of graft-derived TCRγδ cells occurred, indicating that extrathymic IL-7 did not support TCRγδ IEL generation from newborn thymic precursors. In contrast, TCRγδ IEL development occurred efficiently in adult, thymectomized, irradiated C57BL/6J mice reconstituted with IL-7−/− bone marrow. This demonstrated that extrathymic development of TCRγδ IEL required extrathymic IL-7 production. Thus, intrathymic IL-7 was required for development of thymic TCRγδ cells, while peripheral IL-7 was sufficient for development of extrathymic TCRγδ IEL.