Low-Dose IL-2 Signaling Is Specifically Impaired in Regulatory T Cells from T1D Patients

Background: The response to interleukin-2 (IL-2) is essential for the stability and function of regulatory T cells (Tregs) in vivo . Impaired IL-2 receptor signaling might play a crucial role in the decreased function of Tregs in autoimmunity but might also contribute to the increased suppressive capacity of Tregs in cancer. In this study we aimed to examine differences in the phosphorylation of STAT5 as a downstream measure of IL-2 signaling in type 1 diabetes (T1D), rheumatoid arthritis (RA), colo-rectal cancer (CRC) and healthy controls. Material and Methods: Phosphorylation of STAT5 was quantified in 10 T1D, 10 RA, 10 CRC and 10 healthy control samples. Freshly drawn whole blood was stimulated with increasing amounts of IL-2 [0, 0.5, 1, 5, 10 U/ml] for 30 minutes. The expression of phosphorylated STAT5 (pSTAT5) in Tregs was quantified by flow cytometry. Results: Tregs from T1D patients showed significantly decreased levels of pSTAT5 when compared to healthy controls after stimulation with 0.5 U IL-2 (mean fluorescence intensity, MFI: 896 ± 502 vs. 3435 ± 1035, p Conclusion: The response towards low doses of IL-2 is significantly decreased in Tregs from T1D and RA patients. This might contribute to the loss of tolerance and increased autoimmunity in those diseases. However, low dose IL2 signaling does not seem to be involved in the increased suppressive capacity of Tregs in CRC patients. Disclosure B. Prietl: None. S. Kofler: None. S. Stanzer: None. B.M. Obermayer-Pietsch: None. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. H. Sourij: Speaker9s Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc..