CD28超竞争单抗对大鼠原位气管移植术后早期免疫炎性损伤的影响

Effects of CD28 superagonist antibody on immune inflammatory reaction early after orthotopic tracheal transplantation in rats

目的:研究大鼠原位气管移植术后应用CD28超竞争单抗对在体扩增CD4+CD25+FoxP3+调节性T细胞的效果及对移植气管早期免疫排斥炎性反应的影响。方法:采用大鼠同种异体原位气管移植模型,分2组。治疗组受体移植当天经腹腔注射CD28超竞争单抗JJ316(0.5 mg);对照组注射同型抗体mIgG(0.5 mg)。于术后第5天采用流式细胞仪检测颈部引流淋巴结、脾及外周血单个核细胞中CD4+CD25+FoxP3+T细胞的比率;移植气管进行病理形态学检查。结果:CD28超竞争单抗治疗组较同型抗体mIgG对照组气管闭塞程度、炎症反应细胞浸润及呼吸道上皮损伤情况明显减轻;外周血、脾脏及颈部淋巴结中CD4+CD25+FoxP3+T细胞的比率[(16.9±4.2)%、(14.8±3.6)%、(5.8±1.2)%]高于同型抗体mIgG对照组[(2.8±1.4)%、(3.3±1.3)%、(2.9±0.9)%,P<0.05]。结论:大鼠原位气管移植后在体应用CD28超竞争单抗可减轻术后早期的免疫排斥损伤。

Objective：To investigate the effects of superagonistic CD28-specific monoclonal antibody JJ316（supCD28 MAb） on in vivo proliferation of rat CD4＋CD25＋Fox P3＋ Treg（Treg） cells and on allograft rejection reaction in a rat orthotopic tracheal transplantation model.Methods：Rat orthotopic tracheal transplantation models were divided into two groups in the present study.The experimental group was treated with supCD28 MAb（0.5 mg/rat） via intraperitoneal injection on the day of transplantation.Control group was injected with mIgG（0.5 mg/rat）.The proportions of CD4＋CD25＋ FoxP3＋ T cell population in cervical lymph nodes,spleen and peripheral blood monocytes were examined by flow cytometry 5 days after operation.The tracheas were also harvested for histological evaluation.Results：The allografts of the experimental group showed greatly improved airway obliteration,infiltration of inflammatory cells,and respiratory epithelial injury compared with those of the control group.Furthermore,The experimental group had significantly increased CD4＋CD25＋ FoxP3＋ Treg cell population in the lymph nodes,spleen and peripheral blood monocytes compared with those in the supCD28 MAb group（[5.8±1.2]% vs [16.9±4.2]%,[14.8±3.6]%,and [2.9±0.9]%,[3.3±1.3]% vs [2.8±1.4]%,respectively,P〈0.05）.Conclusion：SupCD28 MAb can attenuate airway inflammation injury after orthotopic tracheal transplantation.