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Keywords:

  • CD4+CD45RAFoxP3high activated Treg;
  • FoxP3;
  • fulminant type 1 diabetes;
  • sCTLA-4;
  • type 1A diabetes

Summary

Accumulating lines of evidence have suggested that regulatory T cells (Tregs) play a central role in T cell-mediated immune response and the development of type 1A and fulminant type 1 diabetes. CD4+forkhead box protein 3 (FoxP3)+ T cells are composed of three phenotypically and functionally distinct subpopulations; CD45RA+FoxP3low resting Tregs (r-Tregs), CD45RAFoxP3high activated Tregs (a-Tregs) and CD45RAFoxP3low non-suppressive T cells (non-Tregs). We aimed to clarify the frequency of these three subpopulations in CD4+FoxP3+ T cells and the function of a-Tregs with reference to subtypes of type 1 diabetes. We examined 20 patients with type 1A 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-Tregs 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-Tregs was significantly higher in type 1A diabetes, but not in fulminant type 1 diabetes, than the controls. Further, the proportion of a-Tregs among CD4+FoxP3+ T cells was significantly higher in patients with type 1A diabetes with detectable C-peptide but not in patients with type 1A diabetes without it and with fulminant type 1 diabetes. A proliferation suppression assay showed that a-Tregs were functionally impaired both in fulminant type 1 diabetes and in type 1A diabetes. In conclusion, a-Tregs were functionally impaired, related to residual insulin-secreting capacity and may be associated with the development of type 1 diabetes.