In Vivo Availability of the Cytokine Il-7 Constrains the Survival and Homeostasis of Peripheral ιNKT Cells

Understanding the homeostatic mechanism of invariant natural killer T (ιNKT) cells is a critical issue in ιNKT cell biology. Because IL-15 is required for the thymic generation of ιNKT cells, IL-15 has also been considered necessary for the homeostasis of peripheral ιNKT cells. Here, we delineated the in vivo cytokine requirement for ιNKT cells, and we came to the surprising conclusion that IL-7, not IL-15, is the homeostatic cytokine for ιNKT cells. Employing a series of experimental mouse models in which the availability of IL-7 or IL-15 were manipulated in peripheral tissues, either by genetic tools or by adult thymectomy and cytokine pump installation, we demonstrate that the abundance of IL-7, and not IL-15, limits the size of the peripheral ιNKT cell pool. These results establish a new cytokine requirement for ιNKT cells and reveal a previously unappreciated competition for IL-7 between ιNKT cells and conventional αβ T cells.