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-cellmediated 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+CD25high 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+CD25high T cells were also stained for additional markers HLA-DR, CD69, and CD62L. As NKT cell markers, we used CD161, V?11, and V?24. The frequency of CD4+CD25highHLA-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+CD25highHLA-DR? and CD4+CD25highCD69? 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+V?11+ or V?24+V?11+ NKT cells were similar in all three groups of children studied. Interestingly, children with only two autoantibodies had a higher level of CD161+V?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
regulatory t cells type 1 diabetes nkt cells autoantibody-positive