IL-15 in the life and death of lymphocytes: immunotherapeutic implications

Interleukin (IL)-2 and IL-15 play contrasting roles in the life and death of lymphocytes. IL-2 favors the death of self-reactive lymphocytes to yield self-tolerance, whereas IL-15 favors the survival of memory CD8+ T cells. The actions of IL-15 on memory cell persistence and its inhibition of the immunological checkpoint, activation-induced cell death, enable the maintenance of long-lasting immune responses to vaccines. This supports our view that IL-15 should be used in lieu of IL-2 in the treatment of cancer and as a component of vaccines for cancer and AIDS. Furthermore, we suggest that IL-15 plays a major role in the pathogenesis of autoimmune diseases and propose that therapy involving monoclonal antibodies directed at the IL-15 receptor be evaluated in the treatment of such disorders.