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-2Ra, 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.
Waldmann
Thomas A
TA
Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1374, USA. twald@helix.nih.gov
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; C508024:IL15RA protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2