T regulatory lymphocytes in type 1 diabetes: Impaired CD25 expression and IL-2 induced STAT5 phosphorylation in pediatric patients

Abstract

T regulatory cells (Tregs) are essential for maintaining tolerance and preventing autoimmune diseases, such as type 1 diabetes (T1D). In our study, we investigated CD25 + FoxP3 + Tregs and thymic FoxP3 + Helios + Tregs in large cohorts of children with T1D at onset and with long-term T1D, and further in their relatives and healthy controls. We observed significantly decreased numbers of CD25 + FoxP3 + Tregs, but not FoxP3 + Helios + Tregs, in long-term patients compared with the control group and T1D onset. Furthermore, long-term T1D patients exhibited highly significant decrease of CD25 expression on both CD25 + FoxP3 + Tregs and FoxP3 + Helios + Tregs, independently on age or the duration of diabetes. A similar reduction of CD25 expression was also found in T1D relatives, more significant in those with positive autoantibodies. Low CD25 expression was associated with impaired signal transducer and activator of transcription 5 (STAT5) phosphorylation after IL-2 exposure. Our results show that the frequency of Tregs is altered in a large cohort of long-term T1D patients, a profound decrease in CD25 expression and altered IL-2 signaling are typical features of Tregs populations in long-term diabetic patients and their relatives.

Keywords:

• Type 1 diabetes
• regulatory T cells
• FoxP3
• CD25
• pSTAT5

Acknowledgements

The authors confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All the authors have approved the manuscript and agree with its submission to Autoimmunity.

Z. P. analyzed data and wrote the manuscript.

J. K. designed and performed research, analyzed data, and wrote the manuscript.

K. D., E. D., and K.S. performed research.

Z. S. and S. K. researched data, contributed to the discussion, and edited the manuscript.

J. L. reviewed the manuscript and contributed to the discussion.

K. S. contributed to the discussion and edited the manuscript.

A. S. designed research and wrote the manuscript

Declaration of interest

None of the authors have declared any financial or commercial conflict of interest. The study was supported by the Grant Agency of Czech Republic GACR P302/10/1679, by the Internal Grant Agency of the Czech Ministry of Health IGA NT/11407-5 and by the Czech Ministry of Health AZV 16-32838A.