title: Interleukin 2 in the pathogenesis and therapy of type 1 diabetes.
abstract: Regulatory T cells (Tregs) play a major role in controlling effector T cells (Teffs) responding to self-antigens, which cause autoimmune diseases. An improper Treg/Teff balance contributes to most autoimmune diseases, including type 1 diabetes (T1D). To restore a proper balance, blocking Teffs with immunosuppressants has been the only option, which was partly effective and too toxic. It now appears that expanding/activating Tregs with low-dose interleukin-2 (IL-2) could provide immunoregulation without immunosuppression. This is particularly interesting in T1D as Tregs from T1D patients are reported as dysfunctional and a relative deficiency in IL-2 production and/or IL-2-mediated signaling could contribute to this phenotype. A clinical study of low-dose IL-2 showed a very good safety profile and good Treg expansion/activation in T1D patients. This opens the way for efficacy trials to test low-dose IL-2 in prevention and treatment of T1D and to establish in which condition restoration of a proper Treg/Teff balance would be beneficial in the field of autoimmune and inflammatory diseases.
authors.affiliation: Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), AP-HP, Hôpital Pitié-Salpêtrière, 83 Boulevard de l'Hôpital, 75651, Paris, France, michelle.rosenzwajg@upmc.fr.
authors.forename: Michelle
authors.initials: M
authors.lastname: Rosenzwajg
authors.forename: Guillaume
authors.initials: G
authors.lastname: Churlaud
authors.forename: Agnès
authors.initials: A
authors.lastname: Hartemann
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
mesh_terms: D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000378:metabolism* / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D007376:Interleukin-2