Differences of Circulating CD25(hi) Bregs and Their Correlations with CD4 Effector and Regulatory T Cells in Autoantibody-Positive T1D Compared with Age-Matched Healthy Individuals

Circulating CD25(hi) B cells, a subset of regulatory B cells in humans, are closely related to inflammation and autoimmune diseases. This study is aimed at investigating the alternation of CD25(hi) Bregs and their correlation with CD4 effector and regulatory T cells in T1D individuals. We included 68 autoantibody-positive T1D and 68 age-matched healthy individuals with peripheral blood mononuclear cells (PBMCs) and assessed them with CD25(hi) Bregs and CD4 effector or regulatory T cells by flow cytometry. Here, we demonstrate that the frequency of CD25(hi) Bregs was significantly decreased in T1D subjects (P=0.0016), but they were not affected by disease status (age at T1D diagnosis or duration) or T1D risk loci (rs2104286 or rs12251307) in IL2RA (all P > 0.05). Moreover, higher IgD (P=0.043) and lower CD27 (P=0.0003) expression was observed in CD25(hi) Bregs of T1D individuals, but not the expression of IgM, CD24, or CD38 (all P > 0.05). Although there was no correlation between CD25(hi) Bregs and CD4 effector T cell subsets in either T1D or healthy individuals (all P > 0.05), we found a positive correlation between CD25(hi) Bregs and CD4 Tregs in healthy controls (Sp. r=0.3544, P=0.0249), which disappeared in T1D subjects (Sp. r=0.137, P=0.401). In conclusion, our results suggest that decreased CD25(hi) Bregs and alternation of their phenotypes are features of T1D regardless of disease duration and T1D genetic risk loci, and an impaired balance between CD25(hi) Bregs and CD4 Tregs might contribute to the pathogenesis of T1D.