供体特异性输血通过CD47-SIRPα信号负调控树突状细胞诱导移植耐受  

Preventing Activation of Dendritic Cells through Donor CD47 and Recipient Signal-Regulatory Protein-α Interaction

作　　者：吴小剑[1] 何晓生[1] 吴现瑞[1] 金常光 杨永广[3] 兰平[1] 

机构地区：[1]中山大学附属第六医院(附属胃肠肛门医院)结直肠外科,广东广州510655 [2]辽河油田中心医院呼吸内科,辽宁盘锦124010 [3]哈佛大学麻省总医院器官移植生理研究中心,波士顿02129

出　　处：《中山大学学报（医学科学版）》2010年第6期807-812,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：中山大学医科青年教师科研启动基金(3171913)

摘　　要：【目的】探讨CD47-SIRPα信号在供体特异性输血诱导移植耐受中的作用及其机制。【方法】将受体bm1小鼠按不同的移植前预处理分为3组:CD47WT-DST组、CD47KO-DST组、Non-DST组。7d后移植CD47WT/B6皮片,比较3组皮肤移植物的存活时间;DST后5、24h行流式细胞术检测各组受体抗原呈递细胞的活化情况;DST后5、24h行流式细胞术和组织免疫学检测供体细胞在受体组织内的分布和存活情况。【结果】CD47WT-DST组的皮肤移植物存活时间[MST=(46.77±20.01)d]明显比Non-DST组延长(P<0.0001),而CD47KO-DST组明显加快皮肤移植物排斥反应,其皮肤移植物存活时间[MST=(13.73±4.56)d]甚至比Non-DST组还短(P<0.05)。行CD47KO-DST的受体小鼠体内,DC上CD86的表达水平明显高于CD47WT-DST组和Non-DST组(在5h,P<0.01;在24h,P<0.001)。同样,I-Ab(MHC-Ⅱ)表达水平在CD47KO-DST的受体小鼠体内也明显高于CD47WT-DST和Non-DST组(在5h,P<0.01;在24h,P<0.05)。CD47KO的供体脾细胞在受体内很快被受体清除。【结论】DST诱导耐受作用中供体细胞表达CD47是必需的,供受体间的CD47-SIRPα引发负性调节信号,负反馈调控DC的成熟和活化,抑制其抗原呈递作用,进而诱导供体特异性耐受。【Objective】 To determine possible mechanism of donor CD47 and recipient signal-regulatory protein-α interaction on allograft tolerance induction by donor-specific transfusion. 【Methods】 Groups of bm1 mice were randomized to undergo CD47 WT-DST,CD47 KO-DST and Non-DST control. All animals also received skin allograft 7 days later and compared the survival of skin graft in these 3 groups. Then,selected bm1 recipients were sacrificed at the indicated time points after DST. Nucleated cells were harvested,assessed the expression of the activation marker （ie.,CD80,CD86,and MHC class Ⅱ） on recipient CD11c＋ cells in the different groups by flow cytometric analysis,and checked the distribution of CD47 WT and KO donor cells in lymph nodes,spleen of bm1 recipients at 5 h and 24 h post-DST by flow cytometric analysis and histologic analysis. 【Results】 CD47 WT-DST significantly prolonged skin graft survival （MST = 46.77 ± 20.01 days） compared to that in Non-DST group （MST = 19.75 ± 3.15 days） （P 0.0001）. However,bm1 mice receiving CD47 KO-DST rejected donor skin quickly,and the survival ofdonor skin grafts in this group （MST = 13.73 ± 4.56 days） was even shorter than that in Non-DST group （P = 0.025）. CD86 and MHC class Ⅱ were significantly enhanced on DCs in bm1 recipients of CD47 KO-DST compared to that in CD47 WT-DST recipients. CD47 KO splenocytes are rapidly cleared by recipients after injection as DST. 【Conclusions】 CD47 expression on donor cells is required for tolerance induction by DST. The underlying mechanism of allograft acceptance after DST may be：CD47-SIRPα signaling plays an important role in maintaining the immature or semimature state of recipient DCs after DST,which is needed for inducing T cell tolerance.

关 键 词：供体特异性输血 树突状细胞 皮肤移植 免疫耐受 

分 类 号：R350[医药卫生—基础医学]