Extension of the CD4⁺Foxp3⁺CD25^−/low regulatory T-cell subpopulation in type 1 diabetes mellitus

Abstract

Regulatory T-cells (T_reg) have a crucial role in limiting physiologic autoreactivity. Foxp3 is a master regulator transcription factor of T_reg differentiation and active T_reg cells express high levels of IL-2 receptor α-chain (CD25). The aim of our study was to assess the key markers of T_reg cell function in type 1 diabetic (T1DM) and control subjects by flow cytometry. The proportion of CD25^−/low cells among CD4⁺Foxp3⁺ T_reg cells was higher in T1DM patients that might suggest a shifted proportion of the incomplete/reserve and the fully active (CD4⁺Foxp3⁺CD25⁺) T_reg cell subpopulations in T1DM, similarly to other T_h1-mediated autoimmune diseases. In addition to the decreased expression of CD25 and CTLA-4 in T1DM patients, a positive correlation was observed between the CD25 expression on CD4⁺ and the CTLA-4 expression in CD8⁻ T-lymphocytes both in the T1DM and in the healthy control group. Our results suggest an impaired balance of CD25⁺ and CD25^−/low T_reg cells in T1DM which might reflect a decreased late phase peripheral T_reg activation even in patients with a mean disease duration of more than a decade.

• Autoreactivity
• CD25
• Foxp3
• immune regulation
• insulitis

Declaration of interest

The authors have no financial or commercial conflicts of interest to disclose.