No Alterations in the Frequency of FOXP3 super(+) Regulatory T-Cells in Type 1 Diabetes

Regulatory T-cells (Tregs) play a critical role in maintaining dominant peripheral tolerance. Previous characterizations of Tregs in type 1 diabetes have used antibodies against CD4 and alpha -chain of the interleukin-2 receptor complex (CD25). This report extends those investigations by the addition of a more lineage-specific marker for Tregs, transcription factor forkhead box P3 (FOXP3), in subjects with type 1 diabetes, their first-degree relatives, and healthy control subjects. With inclusion of this marker, two predominant populations of CD4 super(+)CD25 super(+) T-cells were identified: CD4 super(+)CD25 super(+)FOXP3 super(+) as well as CD4 super(+)FOXP3 super(-) T-cells expressing low levels of CD25 (CD4 super(+)CD25 super(LOW)FOXP3 super(-)). In all study groups, the frequency of CD4 super(+)CD25 super(+)FOXP3 super(+) cells was age independent, whereas CD4 super(+)CD25 super(LOW)FOXP3 super(-) cell frequencies strongly associated with age. In terms of additional markers for delineating cells of Treg lineage, FOXP3 super(+) cells were CD127 super(-) to CD127 super(LOW) whereas CD25 super(+) cells were less restricted in their expression of this marker, with CD127 expressed across a continuum of levels. Importantly, no differences were observed in the frequency of CD4 super(+)CD25 super(+)FOXP3 super(+) T-cells in individuals with or at varying degrees of risk for type 1 diabetes. These investigations suggest that altered peripheral blood frequencies of Tregs, as defined by the expression of FOXP3, are not specifically associated with type 1 diabetes and continue to highlight age as an important variable in analysis of immune regulation.