CD28超抗体对大鼠闭塞性气管病的治疗作用

摘要

目的:研究CD28超抗体对在体扩增调节性T细胞的效果及对大鼠闭塞性气管病的影响.方法:采用大鼠同种异体异位气管移植模型.治疗组受体移植当天经腹腔注射CD28特异性单克隆超抗体JJ316 (0.5 mg);对照组注射同型抗体mIgG (0.5 mg).于术后第7天采用流式细胞仪检测颈部淋巴结单个核细胞中CD4~+CD25~+ T细胞和CD4~+Foxp3~+ T细胞的比率;第21天取出移植气管进行病理形态学检查.结果:术后第7天CD28超抗体治疗组大鼠的颈部淋巴结中CD4~+CD25~+ T细胞及CD4~+Foxp3~+ T细胞的比率(8.5%±3.4%,11.5%±2.7%)均显著高于mIgG对照组(1.8%±1.9%,3.2%±2.1%) (P<0.05);第21天CD28超抗体治疗组较mIgG对照组气管闭塞及上皮损伤程度明显减轻.结论:CD28超抗体可靶向扩增调节性T 细胞,减轻了大鼠闭塞性气管病的管腔闭塞.%Objective:To investigate the effects of superagonistic CD28~- specific monoclonal antibody JJ316 (supCD28 MAb) on preferentially expanded rat CD4~+CD25~+Treg (Treg) cells in vivo and its applicability in obliterative airway disease (OAD).Methods:The heterotopic tracheal transplantation model in rats was used.One group received mIgG-treatment(0.5 mg/rat) as control.The experimental group was treated with supCD28 Mab(0.5 mg/rat) via intraperitoneal injection on the day of transplantation.The changes of Treg cell population in cervical lymph nodes were monitored by flow cytometry after 7 days.Tracheas were harvested after 21 days for further histologic evaluation.Results:SupCD28 MAb administration was revealed with a significant increase in the CD4~+CD25~+ T and CD4~+Foxp3~+ T cells population in cervical lymph nodes compared to treatment with mIgG group on day 7 after transplantation,[8.5%±3.4% and 11.5%±2.7% (P<0.05 vs mIgG group)in the supCD28 Mab group,1.8%±1.9% and 3.2%±2.1% in the mIgG group,respectively].Furthermore,the allografts from animals treated with supCD28 MAb were significantly less airway obliteration and destruction of the epithelium compared with that of control group animals on day 21 after transplantation.Conclusion:SupCD28 MAb targets expansion of Treg cells and attenuates airway lumen obliteration in rat obliterative airway disease.