The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance

IL-7 is well known as a lymphopoietic cytokine, but recent studies have also identified a critical role for IL-7 in peripheral T cell homeostasis. IL-7 is well poised to serve as a homeostatic cytokine because it is produced by resting stromal cells, the IL-7R is present on most T cells, and IL-7 down-regulates its own receptor. These features allow IL-7 to signal large numbers of resting T cells and to be efficiently used when supplies are limiting. Consistent with this, in normal hosts, IL-7 is required for survival of naive T cell populations, and IL-7 contributes to homeostatic cycling of naive and memory cells. In addition, lymphopenic hosts accumulate increased levels of IL-7, and the supranormal levels are largely responsible for inducing homeostatic peripheral expansion in response to lymphopenia. Thus, IL-7 plays critical and nonredundant roles in both T cell lymphopoiesis and in maintaining and restoring peripheral T cell homeostasis.