Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes.

Aims  To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4+ T cells to the development of Type 1 diabetes (T1D). Methods  Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25+CD4+ T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4+ T cells. Results  There were no significant differences in the proportions of CD25+ CD4+ T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4+ T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. Conclusions  Decreased expression of the PD-1 gene in CD4+ T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings.