Circulating CD4+CD25high Regulatory T Cells and Natural Killer T Cells in Children with Newly Diagnosed Type 1 Diabetes or with Diabetes‐Associated Autoantibodies

Type 1 diabetes is a T-cell-mediated autoimmune disease in which insufficient regulatory mechanisms are perceived to be involved in the pathogenesis. We used flow cytometry to analyze the proportion of CD4+CD2S high regulatory T cells and natural killer T (NKT) cells in peripheral blood obtained from 25 children with newly diagnosed type 1 diabetes, 21 nondiabetic subjects positive for two or more diabetes-associated autoantibodies, and from 39 autoantibody-negative age- and HLA-matched control subjects. CD4+CD25 high T cells were also stained for additional markers HLA-DR, CD69, and CD62L. As NKT cell markers, we used CD161, Vβ11, and Va24. The frequency of CD4+CD25 high HLA-DR - T cells was significantly higher in multiple autoantibody-positive children than in controls (P = 0.021). We also detected a significantly higher level of CD4+CD25 high HLA-DR - and CD4+CD25 high CD69 - T cells among children expressing three to four autoantibodies when compared to the controls (P = 0.004 and P = 0.048, respectively). The proportions of CD161 + Vβ11 + or Vα24 + Vβ11 + NKT cells were similar in all three groups of children studied. Interestingly, children with only two autoantibodies had a higher level of CD161 + Vβ 11 + NKT cells than the controls (P = 0.002). Our data might be interpreted as indicative of an intensified regulatory response of regulatory T cells and NKT cells during the preclinical phase of the disease.