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

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Grinberg-Bleyer, Yenkel | Baeyens, Audrey | You, Sylvaine | Elhage, Rima | Fourcade, Gwladys | Grégoire, Sylvie | Cagnard, Nicolas | Carpentier, Wassila | Tang, Qizhi | Bluestone, Jeffrey | Chatenoud, Lucienne | Klatzmann, David | Salomon, Benoit | Piaggio, Eliane

Edité par CCSD ; Rockefeller University Press -

International audience. 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 gamma 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.

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