分泌IL-10的B细胞在HIV-1/SIV疾病进程中的动态变化及作用  

Dynamic changes and effects of IL-10 secretion B cells during the progression of HIV-l/SIV disease

作　　者：刘本波 赵明亮 张明旭[2] 肖裕 郑永唐[2] 田仁荣[2] LIU Benbo;ZHAO Mingliang;ZHANG Mingxu;XIAO Yu;ZHENG Yongtang;TIAN Renrong*(College of Pharmacy,Dali University,Dali 671000;Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223;Medical School,Kunming University of Science and Technology,Kunming 650500,China)

机构地区：[1]大理大学药学院,云南大理671000 [2]中国科学院昆明动物研究所,中国科学院动物模型与人类疾病机理实验室,云南昆明650223 [3]昆明理工大学医学院,云南昆明650500

出　　处：《细胞与分子免疫学杂志》2022年第5期391-399,共9页Chinese Journal of Cellular and Molecular Immunology

基　　金：云南省基础研究计划项目(2019FA041,2016FB134)。

摘　　要：目的探讨猴免疫缺陷病毒mac239(SIVmac239)感染的中国猕猴动物模型中分泌IL-10的B细胞(B10细胞)的动态变化及其在AIDS疾病进程中的作用。方法采用流式细胞术检测SIVmac239感染的中国猕猴中CD4+T细胞、CD8+T细胞及B细胞数、B10细胞比率、人类白细胞抗原DR(HLA-DR)及KI-67抗原(ki67)的表达,用实时定量PCR检测血浆病毒载量、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)及IL-6的表达,并用SPSS20.0分析B10细胞在病毒感染后的动态变化及其与上述免疫学指标和病毒载量的关联性。结果SIV感染导致B细胞数减少,B细胞活化和增殖增加;SIV感染导致B10细胞比率增加;感染急性期B10细胞比率与其他检测因素关联性不显著,感染慢性期其与CD4^(+)T细胞数、TNF-α表达水平、ki67^(+)CD4^(+)T细胞比率、CTLA4^(+)CD4^(+)T细胞比率、CD4^(+)T细胞功能呈显著负相关,而与病毒载量呈显著正相关,但是其与多数CD8^(+)T细胞参数的关联性均不显著。结论SIV感染慢性期,B10细胞在一定程度上抑制炎症反应的同时也加剧了CD4^(+)T细胞的丢失,从而使得病毒复制失控,疾病进程加速。Objective To investigate the dynamic changes of IL-10 secretion B cells(B10 cells)in SIVmac239-infected Hhesus macaques and the effects of B10 cells in acquired immunodeficiency syndrome progression.Methods Flow cytometry was applied to quantify CD4^(+)and CD8^(+)T lymphocytes,B cells number and the ratio of B10 cells,HLA-DR and ki67 in SIVmac39-infected Rhesus macaques.Real-time quantitative PCR was performed to detect SIV RNA levels and mRNA levels of IL-10,tumor necrosis factor-a(TNF-a)and IL-6.Dynamic changes of B10 cells in SIVmac239-infected Rhesus macaques and correlation analysis was performed with SPSS 20.0.Results SIV led to the reduction of B cells number,and comparatively increased activation and proliferation of B cells.Besides,it also caused an increase of B10 cells ratio in Rhesus macaques.No significant correlation was found between B10 cells ratio and other indicators(including CD4^(+)T cells number,TNF-a mRNA levels,ki67^(+)CD4^(+)T cells ratio,CTLA4^(+)CD4^(+)T cells ratio and CD4^(+)T cells function)in SIV-infected acute phase.However,B10 cells ratio and other indicators were in significantly negative correlation,while B10 cells ratio and SIV RNA levels were in significantly positive correlation in chronic phase.Meanwhile,no significant correlation was found between B10 cells ratio and CD8^(+)T relative indicator Conclusion In chronic phase of SIV-infection,when B10 cells inhibits inflammation response and increases CD4^(+)T cells lose,virus replication gets uncontrolled and consequently leads to accelerated disease progression.

关 键 词：猴免疫缺陷病毒 肿瘤坏死因子α 白细胞介素1Β 实时定量PCR 疾病进程 病毒复制 免疫学指标 B细胞 

分 类 号：R511[医药卫生—内科学] R364.5[医药卫生—临床医学] Q279[生物学—细胞生物学]