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IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells

Regulatory T cells (T reg cells) play a major role in controlling the pathogenic autoimmune process in type 1 diabetes (T1D). Interleukin 2 (IL-2), a cytokine which promotes T reg cell survival and function, may thus have therapeutic efficacy in T1D. We show that 5 d of low-dose IL-2 administration...

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Detalles Bibliográficos
Autores principales: Grinberg-Bleyer, Yenkel, Baeyens, Audrey, You, Sylvaine, Elhage, Rima, Fourcade, Gwladys, Gregoire, Sylvie, Cagnard, Nicolas, Carpentier, Wassila, Tang, Qizhi, Bluestone, Jeffrey, Chatenoud, Lucienne, Klatzmann, David, Salomon, Benoît L., Piaggio, Eliane
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931175/
https://www.ncbi.nlm.nih.gov/pubmed/20679400
http://dx.doi.org/10.1084/jem.20100209
Descripción
Sumario:Regulatory T cells (T reg cells) play a major role in controlling the pathogenic autoimmune process in type 1 diabetes (T1D). Interleukin 2 (IL-2), a cytokine which promotes T reg cell survival and function, may thus have therapeutic efficacy in T1D. We show that 5 d of low-dose IL-2 administration starting at the time of T1D onset can reverse established disease in NOD (nonobese diabetic) mice, with long-lasting effects. Low-dose IL-2 increases the number of T reg cells in the pancreas and induces expression of T reg cell–associated proteins including Foxp3, CD25, CTLA-4, ICOS (inducible T cell costimulator), and GITR (glucocorticoid-induced TNF receptor) in these cells. Treatment also suppresses interferon γ production by pancreas-infiltrating T cells. Transcriptome analyses show that low-dose IL-2 exerts much greater influence on gene expression of T reg cells than effector T cells (T eff cells), suggesting that nonspecific activation of pathogenic T eff cells is less likely. We provide the first preclinical data showing that low-dose IL-2 can reverse established T1D, suggesting that this treatment merits evaluation in patients with T1D.