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

Abstract

Regulatory T-cells (Treg) have a crucial role in limiting physiologic autoreactivity. Foxp3 is a master regulator transcription factor of Treg differentiation and active Treg cells express high levels of IL-2 receptor α-chain (CD25). The aim of our study was to assess the key markers of Treg cell function in type 1 diabetic (T1DM) and control subjects by flow cytometry. The proportion of CD25(-/low) cells among CD4(+)Foxp3(+) Treg cells was higher in T1DM patients that might suggest a shifted proportion of the incomplete/reserve and the fully active (CD4(+)Foxp3(+)CD25(+)) Treg cell subpopulations in T1DM, similarly to other Th1-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) Treg cells in T1DM which might reflect a decreased late phase peripheral Treg activation even in patients with a mean disease duration of more than a decade.

Cells with Treg-specificFOXP3demethylation but low CD25 are prevalent in autoimmunity

“…Although the frequency of FOXP3 + cells in the CD127 low CD25 low subset was compared in T1D patients versus controls in one previous study with no difference observed [13], we note that the number of participants was small: 10 healthy control individuals and 16 patients. In contrast, Zoka et al [18] observed that the proportion of CD25 low cells among FOXP3 + CD4 + T cells is higher in T1D patients than in controls, a phenotype consistent with our observations.…”

Age-dependent divergent effects of OX40L treatment on the development of diabetes in NOD mice

“…Interestingly, increased percentages of this subpopulation in the pancreatic infiltrate has been found to correlate with late stages of inflammation (52). Further, increase in the percentages of a similar subpopulation was also found in T1DM patients (53). This could potentially be a response to lower IL-2 availability concomitant with age.…”

Reduced GLP-1 response to a meal is associated with the CTLA4 rs3087243 G/G genotype

“…Fasting, EDTA-anticoagulated blood samples were collected. The flow cytometric analysis was performed as described in detail in our prior publication [20] using the following flow cytometric antibodies: CD3-PE-Cy7, CD8-PerCP, CD25-AF700 (Biolegend, San Diego, CA, USA), Foxp3-PE-CF594 and CTLA-4-APC (BD Biosciences, San Jose, CA, USA). A Beckman Coulter Navios flow cytometer and version 1.2 of Beckman Coulter Kaluza software (Brea, CA, USA) were used for quantitative analysis.…”