Circulating CD4 super(+)CD25 super(high) Regulatory T Cells and Natural Killer T Cells in Children with Newly Diagnosed Type 1 Diabetes or with Diabetes-Associated Autoantibodies

• Published in: Annals of the New York Academy of Sciences 2007-06, Vol.1107 (1), p.363-372
• Main Authors: Oling, Viveka, Marttila, Jane, Knip, Mikael, Simell, Olli, Ilonen, Jorma
• Format: Article
• Language: English
• Subjects: Autoantibodies
• ISSN: 0077-8923; 1930-6547
• DOI: 10.1196/annals.1381.038

AbstractType 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 super(+)CD25 super(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 super(+)CD25 super(high) T cells were also stained for additional markers HLA-DR, CD69, and CD62L. As NKT cell markers, we used CD161, Vb11, and Va24. The frequency of CD4 super(+)CD25 super(high)HLA-DR super(-) 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 super(+)CD25 super(high)HLA-DR super(-) and CD4 super(+)CD25 super(high)CD69 super(-) 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 super(+)Vb11 super(+) or Va24 super(+)Vb11 super(+) NKT cells were similar in all three groups of children studied. Interestingly, children with only two autoantibodies had a higher level of CD161 super(+)Vb11 super(+) 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.