小剂量抗CD3单克隆抗体有效逆转新发的Ⅰ型糖尿病  

Effective Reversal of New-Onset Type 1 Diabetes by Treatment with Low Dose Anti-CD3 Monoclonal Antibodies

作　　者：陈宇[1] 陈国江 韩根成[2] 王建安[2] 黎燕[2] 

机构地区：[1]浙江大学动物科学学院兽医系 [2]军事医学科学院基础医学研究所分子免疫研究室,北京100850

出　　处：《中国比较医学杂志》2008年第4期47-50,F0003,共5页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(30571732);973(2007CB512406)基金资助项目

摘　　要：目的验证抗CD3单克隆抗体治疗自身免疫病如Ⅰ型糖尿病的可行性,并对机理进行初步探讨。方法以Ⅰ型糖尿病动物模型-非肥胖性糖尿病(nonobese diabetic,NOD)小鼠为研究对象,将新发病的小鼠随机分为治疗组和对照组,分别给予抗CD3抗体和对照抗体,剂量均为5μg/d×5d,监测血糖观察糖尿病的逆转情况。结果经短期小剂量CD3单抗治疗,到第9周时,75%的小鼠的血糖恢复至正常。维持时间超过30周,胰岛形态亦得到了明显改善。CD3单抗的这种效应并不是由于清除T细胞引起免疫抑制所致,而是诱导产生了胰岛β细胞特异性的免疫耐受。结论小剂量抗CD3单克隆抗体治疗可有效逆转新发的Ⅰ型糖尿病。Objective To determine the feasibility of anti-CD3 antibodies in the treatment for autoimmune diseases such as type 1 diabetes and clarify the underlying mechanisms. Methods New-onset diabetic NOD mice were randomly divided into anti-CD3-treated and control groups, and received anti-CD3 and hamster IgG at the dose of 5μg/day × 5 days, respectively. Remission of diabetes was determined by blood glucose test. Results The treatment of short-phase and low-dose anti-CD3 antibodies resulted in the return to normoglycemia in 75 % diabetic NOD mice by nineth week after treatment, keeping over 30 weeks, accompanied with recovery of shape of pancreatic islets. This effect was not attributed to ensuing immunosuppression following depletion of T cells but to induction of specific immune tolerance to pancreatic β cells. Conclusion The treatment of low-dose anti-CD3 antibodies may effectively reverse new-onset autoimmune diabetes.

关 键 词：抗CD3单抗 Ⅰ型糖尿病 NOD小鼠 特异性免疫耐受 

分 类 号：R587.1[医药卫生—内分泌]