供者特异性抗原静脉输注联合抗γ链单克隆抗体诱导小鼠皮肤移植物免疫耐受  

Anti-γc and anti-IL-2Rβ mAbs inhibit donor-antigen reactive T cells proliferation and induce H-Y skin graft acceptance in murine model

作　　者：昌盛[1] 沈世乾[1] 陈必成[1] 杜敦峰[1] 周洁[1] 张鑫[1] 陈忠华 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所教育部器官移植国家重点实验室,武汉430030

出　　处：《中华器官移植杂志》2005年第3期154-156,共3页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金资助项目(30271243)

摘　　要：目的　探讨静脉输注供者特异性抗原联合抗白细胞介素2受体(IL 2R)γ链单克隆抗体诱导移植免疫耐受的可行性。方法　在C57BL/6小鼠建立H Y皮肤移植模型,术前7 d给予5×106个供者脾细胞静脉输注,并分别于术前6 d和4 d给予抗白细胞介素2受体γ链单克隆抗体(4G3、3E12及TUGm2各0.5 mg)和抗IL 2Rβ单克隆抗体(TM β1,0.5 mg)混合液2.0 mg腹腔注射,以单纯行H Y皮肤移植模型和静脉输注供者特异性抗原的H Y皮肤移植模型为对照,观察皮肤移植物的存活时间。结果　联合给予抗白细胞介素2受体γ链单克隆抗体和供者特异性抗原输注组的皮肤移植物存活时间均超过100 d,显著长于单纯H Y皮肤移植组的33.42 d(P<0.01)及仅输注供者特异性抗原H Y皮肤移植组的14.71 d(P<0.01)。结论　在H Y皮肤移植模型中,静脉输注供者特异性抗原联合抗白细胞介素2受体γ链单克隆抗体可以成功地诱导受者对皮肤移植物的免疫耐受。Objective The is an To investigate whether blocking common cytokine receptor γ chain (γc) signals can induce transplant tolerance.Methods The animals were randomly divided into 3 groups ( n =7 in each). GroupⅠ (control group): C57BL/6 female mice only received H-Y skin grafts. Group Ⅱ: Female recipients received transfusion of splenocytes (5×10 6 cells) from syngeneic male mice on day 7 before H-Y skin grafting. Group Ⅲ: Following donor-splenocytes pretreatment, on the day 2 and 4, female recipients received intraperitoneal injection of mixture of anti-IL-2Rβ mAb (TM-β1) and anti-γc mAbs (i.e., 4G3, 3E12 and TUGm2, 0.5 mg , respectively). On the day 7, H-Y skin grafts were performed.Results All recipients treated with mixture of mAbs in combination with donor-splenocytes transfusion accepted H-Y skin grafts over 100 days without evidence of rejection. Group Ⅰ rejected grafts within 35 days after grafting (MST= 33.42 days) and group Ⅱ rejected grafts within 17 days after grafting (MST= 14.71 days). There were statistically significant diffe- rences among the groups ( P < 0.01 ).Conclusion Blockade of γc signaling in combination with donor- splenocytes pretreatment can markedly prolong H-Y skin graft survival, which might be associated with inhibition of antigen-specific T cell proliferation and induction of apoptosis.

关 键 词：皮肤移植 供者 特异性抗原 静脉输注 单克隆抗体 白细胞介素2受体 联合 植物 存活时间 混合液 

分 类 号：R622.1[医药卫生—整形外科]