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

Authors: ÖLING, VIVEKA; MARTTILA, JANE; KNIP, MIKAEL; SIMELL, OLLI; ILONEN, JORMA

Source: Annals of the New York Academy of Sciences, Volume 1107, Number 1, June 2007 , pp. 363-372(10)

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Abstract:

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⁺CD25^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 Vα24. The frequency of CD4⁺CD25^highHLA-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^highHLA-DR⁻ and CD4⁺CD25^highCD69⁻ 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⁺Vβ11⁺ 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.

Keywords: Type 1 diabetes; autoantibody-positive; regulatory T cells; NKT cells

Document Type: Research article

DOI: http://dx.doi.org/10.1196/annals.1381.038

Affiliations: 1: Department of Paediatrics, University of Turku, Turku, Finland

Publication date: 2007-06-01

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

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

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