MODS小鼠脾脏树突细胞PD-1、PD-L1的表达变化及其意义  

PD-1 and PD-L1 expressions in dendritic cells of spleen of mice with MODS and their significance

作　　者：刘茜[1,2] 陆江阳[2] 王晓虹[2] 曲冰杰[2] 李韶然[2] 康佳蕊[2] 

机构地区：[1]军事医学科学院放射与辐射医学研究所八室,北京100850 [2]解放军总医院第一附属医院病理科

出　　处：《解放军医学杂志》2010年第1期17-19,共3页Medical Journal of Chinese People's Liberation Army

基　　金：全军“十一五”医学科研基金(06MB307)

摘　　要：目的观察多器官功能障碍综合征(MODS)小鼠脾脏树突细胞(DC)中负性共刺激分子(PD-1、PD-L1)和CD86、MHC-Ⅱ的表达情况,探讨DC在脓毒症末期免疫抑制中的作用和机制。方法130只C57BL/6小鼠随机分为6h、12h、24h、48h、5-7d、10-12d组和对照组,前6组实验小鼠采用腹腔注射酵母多糖法复制脓毒症-MODS模型(每组20只),对照组(10只)不做处理。观察各组脾脏的病理形态学改变,使用BDIMagTM树突细胞富集磁珠分离出脾脏DC,运用流式细胞仪检测脾脏DC中PD-1、PD-L1、MHC-Ⅱ分子(I-Ab)及CD86的表达变化规律及其与病程的关系。结果24h、48h组和10-12d组实验小鼠脾脏组织结构明显破坏。脾脏DC中PD-L1的表达在病程早期(6h)即明显升高(78.4%±34.5%,P<0.05),而后迅速下降,至24h时恢复至正常水平,5d后再度升高,持续至病程终末的MODS期(10-12d)达到高峰(81.7%±31.8%,P<0.01)。PD-1在脾脏DC中表达量较低,但具有与PD-L1相同的变化趋势。MHC-Ⅱ分子(I-Ab)与CD86在致伤早期(6h)明显升高,24h开始下降,至10-12d时下降至正常水平。结论病程早期脾脏以活化DC增生为主,而在MODS期主要为耐受性DC。耐受性DC中共刺激分子及MHC-Ⅱ分子表达下降,而负性共刺激分子表达明显上调,并可通过PD-L1和PD-1分子抑制T细胞的功能,发挥负向免疫调节作用,诱导免疫抑制形成和MODS的发生。Objective To study the expression of negative co-stimulatory molecules programmed death 1（PD-1）,programmed death 1 ligand（PD-L1）,MHC-Ⅱ（I-Ab）and co-stimulatory molecule CD86 on splenic dendritic cells（DC）in mice with multiple organ dysfunction syndrome（MODS）,and the role of splenic DCs in immunosuppression of sepsis and MODS.Methods One hundred and thirty mice were divided randomly into 7 groups：6h,12h,24h,48h,5-7d and 10-12d groups and normal control group.Sepsis-MODS mouse model was reproduced by injection of zymosan into the peritoneal cavity of mice in 6h,12h,24h,48h,5-7d and 10-12d groups（20 mice each）,and the normal control group（10 mice）received no treatment.Histopathological changes in spleen were studied in H-E sections.After enrichment of DC with BDTM IMag,DC were isolated,and expressions of PD-1,PD-L1,MHC-Ⅱ（I-Ab）and CD86 on splenic DCs were examined by flow cytometry,and its relationships between these expressions and the development of sepsis and MODS were then analyzed.Results The histological structures of spleen were damaged in MODS mice in 24h,48h and 10-12d groups.The expression of PD-L1 increased（78.4%±24.5%,P〈0.05）6h after zymsan injection,and then fell to normal level at 24h and 48h,and it increased again on 5-7d,peaked on 10-12d（81.7%±21.8%,P〈0.01）.The fluctuation of PD-L1 expression level was roughly parallel to that of PD-1.MHC-Ⅱ（I-Ab）and CD86 increased at 6h and 12h,dropped to the normal level on 10-12d.Conclusions In the early stage of injury,splenic DCs are predominantly activated,while in the later stage,tolerant DCs gain the dominance prominently.The tolerant DCs up-regulate the expression of negative co-stimulatory molecule PD-L1 and down-regulate both MHC-Ⅱ molecule and co-stimulatory molecule CD86,giving rise to suppression of the function of T lymphocytes through PD-L1/PD-1 pathway,thus inducing immunosuppression to participate in the pathogenesis of MODS.

关 键 词：多器官功能衰竭 树突细胞 程序性死亡因子1 程序性死亡因子配体1 脾 

分 类 号：R392.32[医药卫生—免疫学]