Increased expression of regulatory T cell-associated markers in recent-onset diabetic children

Abstract

CD4⁺CD25^hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4⁺ CD25^hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4⁺CD25^hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4⁺ CD25^hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4⁺CD25^hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3⁺ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4⁺CD25^hi FOXP3⁺ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4⁺CD25^hi cells could contribute to the development of type 1 diabetes.