Thymic and intestinal intraepithelial T lymphocyte development are each regulated by the gamma c-dependent cytokines II-2, IL-7, and IL-15

Both thymic and extrathymic T lineage development are characterized by cyto kine-dependent regulation of complex proliferative, differentiative, and an ti-apoptotic processes. The role of the gammac-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, t hrough the analysis of double knock-out,nice, which lack signaling through the IL-7R and other gammac-dependent cytokines, we revealed a role for IL-1 5 in the production of early thymic pro-T cells. Although IL-2 does not fun ction in the production of thymocytes, thymic restoration of IL-2R expressi on prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mi ce, suggesting that IL-2R functions non-redundantly at the level of the thy mus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also exten d their developmental effects beyond the thymus to other sites of T lymphoc yte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically div erse subsets of intestinal intraepithelial lymphocytes.