CD 4 + CD 45 RA − F ox P 3 high activated regulatory T cells are functionally impaired and related to residual insulin‐secreting capacity in patients with type 1 diabetes

Summary Accumulating lines of evidence have suggested that regulatory T cells ( T regs ) play a central role in T cell‐mediated immune response and the development of type 1 A and fulminant type 1 diabetes. CD 4 + forkhead box protein 3 ( F ox P 3) + T cells are composed of three phenotypically and functionally distinct subpopulations; CD 45 RA + F ox P 3 low resting T regs (r‐ T regs ), CD 45 RA − F ox P 3 high activated T regs (a‐ T regs ) and CD 45 RA − F ox P 3 low non‐suppressive T cells (non‐ T regs ). We aimed to clarify the frequency of these three subpopulations in CD 4 + F ox P 3 + T cells and the function of a‐ T regs with reference to subtypes of type 1 diabetes. We examined 20 patients with type 1 A diabetes, 15 patients with fulminant type 1 diabetes, 20 patients with type 2 diabetes and 30 healthy control subjects. A flow cytometric analysis in the peripheral blood was performed for the frequency analysis. The suppressive function of a‐T regs was assessed by their ability to suppress the proliferation of responder cells in a 1/2:1 co‐culture. A flow cytometric analysis in the peripheral blood demonstrated that the frequency of a‐ T regs was significantly higher in type 1 A diabetes, but not in fulminant type 1 diabetes, than the controls. Further, the proportion of a‐ T regs among CD 4 + F ox P 3 + T cells was significantly higher in patients with type 1 A diabetes with detectable C ‐peptide but not in patients with type 1 A diabetes without it and with fulminant type 1 diabetes. A proliferation suppression assay showed that a‐ T regs were functionally impaired both in fulminant type 1 diabetes and in type 1 A diabetes. In conclusion, a‐ T regs were functionally impaired, related to residual insulin‐secreting capacity and may be associated with the development of type 1 diabetes.