Ryba Monika, Hak Lukasz, Zorena Katarzyna, Myśliwiec Małgorzata, Myśliwska Jolanta
Zaklad Immunologii Uniwersytetu Medycznego w Gdansku.
Pediatr Endocrinol Diabetes Metab. 2010;16(1):12-6.
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.
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.
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.
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)].
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.
一部分自然产生的调节性T淋巴细胞中的定量和/或定性功能障碍可能会影响自身免疫性疾病的发展，包括1型糖尿病。CD62L是一种归巢受体，可将T淋巴细胞导向淋巴结。对非肥胖糖尿病（NOD）小鼠进行的研究表明，表达CD62L的调节性T细胞耗竭会导致糖尿病，只有高表达CD62L的调节性T细胞能够预防该病。
本文旨在分析1型糖尿病患儿外周血中以及在抗TNF抗体体外刺激后表达CD62L的调节性T淋巴细胞亚群。
对55例1型糖尿病患者进行了检查。糖尿病组的疾病平均病程为6.45（±3.7）年。使用流式细胞术评估糖尿病患者外周血中以及在抗CD3（对照）、抗CD3联合抗TNF和抗CD3联合TNF体外刺激后的调节性T细胞和携带CD62L的调节性T细胞的百分比。
与健康对照相比，1型糖尿病患者的调节性T细胞和表达CD62L亚群的调节性T细胞百分比更低。此外，这些细胞对抗CD3抗体刺激的反应与健康个体的细胞不同。抗TNF诱导CD4+Foxp3+和CD4+Foxp3+CD62L高表达调节性T细胞的百分比显著增加。用TNF-α处理后，这些细胞的频率显著降低。在糖尿病组中，我们发现CD4+CD25高表达CD62L高表达T淋巴细胞与糖化血红蛋白（HbA1c）[r =（-0.25）]以及C反应蛋白（CRP）水平[r =（-0.38）]之间呈负相关。
调节性T细胞和高表达CD62L的调节性T细胞百分比降低可能导致1型糖尿病期间促炎细胞因子产生的抑制无效。我们提出抗TNF对1型糖尿病患者调节性T细胞亚群的保护作用，并强调促炎细胞因子TNF-α的重要性，它可能是这些患者调节性T细胞亚群数量异常的原因。
