Type 1 diabetes is an autoimmune disease where autoreactive T lymphocytes destroy pancreatic beta cells. We previously reported a defect in CD4⁺ Tregs cell proliferation and reduced CD4⁺ Tregs PD-1 expression in patients. Another ‘memory-like’ regulatory subset, CD8⁺ Tregs, evaluated as CD8⁺CD25⁺FOXP3⁺, has recently raised interest for their effective suppressive activity. Different CD8⁺ T cell populations, their proliferation capacity and expression of PD-1 molecule were evaluated by flow-cytometer analysis in newly diagnosed, long-term Type 1 diabetes patients compared to healthy normal donors. Under basal conditions, CD8⁺ Tregs and CD8⁺ Teffs were seemingly represented among study groups while there was evidence of diminished expression of PD-1 in Teff subsets of long-term patients. After 3 days of PMA/ionomycin stimulation, patients CD8⁺ Tregs showed decreased percentage in respect to control group. CD8⁺ Teffs were instead increased in long-term diabetics versus controls. PD-1⁺CD8⁺ Tregs were represented at a much lower percentage in long-term diabetic patients, in respect to controls. Importantly, patients CD8⁺ Tregs and CD8⁺ Teffs presented a significant proliferation defect in respect to the control group. In conclusion, our study indicates that a defect of CD8⁺ Tregs is observed in diabetics. This subset could thus represent a novel target of immunotherapy in patients.

1型糖尿病是一种自身免疫性疾病，其中自身反应性T淋巴细胞破坏了胰腺β细胞。我们先前曾报道CD4 ⁺ Tregs细胞增殖存在缺陷，并降低了患者的CD4 ⁺ Tregs PD-1表达。另一个“记忆样”调节子集CD8 ⁺ Tregs被评估为CD8 ⁺ CD25 ⁺ FOXP3 ⁺，最近因其有效的抑制活性而引起了人们的兴趣。通过流式细胞仪分析，与健康的正常捐献者相比，通过新的长期诊断的1型糖尿病患者，通过流式细胞仪分析了不同的CD8 ⁺ T细胞群体，其增殖能力和PD-1分子的表达。在基础条件下，CD8 ⁺Tregs和CD8 ⁺ Teffs似乎代表了研究组，而有证据表明长期患者的Teff亚型中PD-1的表达减少。在PMA /离子霉素刺激3天后，患者CD8 ⁺ Tregs相对于对照组显示出降低的百分比。与对照相比，长期糖尿病患者的CD8 ⁺ Teffs升高。与对照组相比，长期糖尿病患者中PD-1 ⁺ CD8 ⁺ Treg的百分比要低得多。重要的是，患者CD8 ⁺ Treg和CD8 ⁺与对照组相比，Teffs表现出明显的增殖缺陷。总之，我们的研究表明在糖尿病患者中观察到CD8 ⁺ Treg的缺陷。因此，该子集可以代表患者中免疫疗法的新靶标。