title: CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2.
abstract: CD4+CD25+ T regulatory (Treg) cells control immunologic tolerance to self-antigens and play a role in suppressing antitumor immune responses, but the mechanism of suppression in vivo remains uncertain. Recently, signaling through the high-affinity interleukin-2 (IL-2) receptor has been shown to be critical for Treg cell differentiation and survival in vivo. Mice deficient in IL-2 or its receptor (CD25 or CD122) or deficient in downstream signaling molecules, including JAK-3 and STAT-5, do not develop a stable population of Treg cells and subsequently acquire lymphoproliferative disease and autoimmunity. in vitro, IL-2 is required to expand Treg cells and to induce their suppressive characteristics. Conversely, IL-2-based regimens can activate cellular antitumor immunity and are the mainstay of immunotherapies directed against melanoma and kidney cancers. Given the seemingly disparate effects of IL-2, the authors discuss the possibility that IL-2 may not be the optimal T-cell growth factor in vivo, but rather an inducer of self-tolerance. The authors propose that other gamma c-signaling cytokines, including IL-15, may be alternative choices for the immunotherapy of cancer.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Mark O. Hatfield Clinical Research Center, Bethesda, Maryland 20892, USA. Paul_Antony@nih.gov
authors.forename: Paul Andrew
authors.initials: PA
authors.lastname: Antony
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D008232:Lymphoproliferative Disorders / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2
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