Introduction: Quantitative and/or qualitative dysfunctions in a subset of naturally arising regulatory T lymphocytes may have impact on autoimmune disease development, including diabetes type 1. CD62L is a homing receptor that directs T lymphocytes to lymph nodes. Studies conducted on NOD mice showed that depletion of Tregs expressing CD62L results in diabetes and only CD62Lhigh Tregs are able to protect against the disease.
Aim of the study: The purpose of the paper was to analyze the regulatory T lymphocyte subset with CD62L expression in children with diabetes type 1 in peripheral blood and after in vitro stimulation with anti-TNF antibody.
Material and methods: 55 patients with diabetes type 1 were examined. Mean duration of the disease in the diabetic group was 6.45 (+/-3.7) years. The percentage of Tregs and Tregs carrying CD62L was evaluated using flow cytometry in peripheral blood of diabetic patients as well as after in vitro stimulation with the anti-CD3 (control), the anti-CD3 with the anti-TNF and anti-CD3 with TNF.
Results: Diabetic type 1 patients were characterized by a lower percentage of Tregs and Tregs expressing CD62L subset compared to their healthy counterparts. In addition, these cells reacted differently to anti-CD3 antibody stimulation than the cells from the healthy individuals. Anti-TNF induced a significant increase in the percentage of CD4+Foxp3+ and CD4+Foxp3+CD62Lhigh regulatory T cells. After treatment with TNF-alpha the frequency of these cells significantly decreased. In the diabetic group we showed a negative correlation between CD4+CD25highCD62Lhigh T lymphocytes and HbA1c [r=(-0.25)] as well as CRP level [r=(-0.38)].
Conclusions: The lower percentage of Tregs and CD62Lhigh Tregs may contribute to ineffective suppression of proinflammatory cytokine production during type 1 diabetes. We suggest the protective role of anti-TNF on Treg subset in diabetic type 1 patients and we highlight the importance of proinflammatory cytokine - TNF-alpha, which may be responsible for quantitative abnormalities in Treg subset in these patients.