The IL-2/IL-15 Receptor Systems: Targets for Immunotherapy

Although interleukin-2 (IL-2) and -15 (IL-15) share two receptor subunits and many functions, at times they provide contrasting contributions to T-cell-mediated immune responses. IL-2, through its pivitol role in activation-induced cell death (AICD), is involved in peripheral tolerance through the elimination of self-reactive T cells. In contrast, in general IL-15 manifests antiapoptotic actions and inhibits IL-2-mediated AICD. IL-15 stimulates persistence of memory phenotype CD8+ T cells, whereas IL-2 inhibits their expression. Humanized monoclonal antibodies that recognize IL-2Rα, the private receptor for IL-2, are being employed to inhibit allograft rejection and to treat T-cell leukemia/lymphoma. Therapies directed toward inhibiting the actions of the inflammatory cytokine, IL-15, are proposed for an array of autoimmune disorders as well as diseases associated with the retrovirus human T-cell lymphotrophic virus 1.