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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
牛永胜,曹浩,刘刚,史乾,范慧敏*,刘中民*
0
(同济大学附属东方医院心胸外科研究室,上海 200120)
摘要:
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。
关键词:  气管移植  移植耐受  调节性T淋巴细胞  CD28抗原
DOI:10.3724/SP.J.1008.2009.01236
投稿时间:2009-03-04修订日期:2009-09-16
基金项目:国家自然科学基金 (30772150,30872557).
Effects of CD28 superagonist antibody on immune inflammatory reaction early after orthotopic tracheal transplantation in rats
NIU Yong-sheng,CAO Hao,LIU Gang,SHI Qian,FAN Hui-min*,LIU Zhong-min*
(Department of Cardiovascular and Thoracic Surgery,East Hospital,Tongji University,Shanghai 200120,China)
Abstract:
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.
Key words:  tracheal transplantation  transplantation tolerance  regulatory T-lymphocytes  CD28 antigens