CD 127(-) and FoxP3(+) expression on CD25(+)CD4(+) T regulatory cells upon specific diabetogeneic stimulation in high-risk relatives of type 1 diabetes mellitus patients
Abstract
Abnormalities in CD4(+)CD25(+) regulatory T cells (Treg) may contribute to type 1 diabetes (T1D) development. First-degree relatives of T1D patients are at increased risk especially when they carry certain HLA II haplotypes.
Using two novel markers of CD4(+)CD25(+) Treg (CD127(-) and FoxP3(+) respectively), we evaluated number and function of Treg after specific stimulation with diabetogeneic autoantigens in 11 high-risk (according to HLA-linked risk) relatives of T1D patients and 14 age-matched healthy controls using a cytokine secretion assay based on interferon-gamma (IFN-gamma) production. High-risk relatives of T1D patients had significantly lower pre- and post-stimulatory number of CD127(-) Treg than that of healthy controls (P < 0.05).
Labelling Treg with FoxP3(+) demonstrated similar trend but did not reach statistical significance. Although the stimulation with diabetogenic autoantigens did not lead to a significant change in number of Treg in both groups, the defective function of Treg was performed by significantly higher activation of diabetogeneic T cells in high-risk relatives of T1D patients compared to healthy controls (P <= 0.02).
Individuals at increased HLA-associated genetic risk for T1D showed defects in Treg.