从中国恒河猴感染猴免疫缺陷病毒后的不同进展情况看艾滋病的发病机制  

Comparison of bio-medical parameters in SIV infected Chinese rhesus monkeys with diverse progres-sion correlated to the pathogenesis of simian AIDS

作　　者：吴小闲[1] 卢耀增[1] 陈颂[2] 潘菊华[3] 王阶[3] 黄世敬[3] 赖春辉[2] 郭卫中[2] 孙丽华[1] 徐艳峰[1] 鲍琳琳[1] 卢葳[4] 

机构地区：[1]中国医学科学院/北京协和医学院医学实验动物研究所,100021 [2]广州中医药大学热带医学研究所 [3]中国中医科学院广安门医院 [4]法国发展研究院-UMI233中国部/广州中医药大学热带医学研究所

出　　处：《中华微生物学和免疫学杂志》2012年第6期496-503,共8页Chinese Journal of Microbiology and Immunology

摘　　要：目的中国恒河猴感染猴免疫缺陷病毒（SIV）后，根据其病毒载量水平、疾病进程速度等，可分为普通进展型（NP）、快速进展型（RP）以及长期不进展型（LTNP）／精英控制者（Ec）等3类。对属于不同进展类型的动物的各项参数进行比较，有助于进一步理解AIDS的发病机制。方法使用SIVmae239毒株静脉感染中国恒河猴后，定期采血进行血液学、免疫学、病毒学及病理学检查；并对各参数进行比较。结果16只感染动物中，有1例动物（RM449猴）快速进展并死亡于感染后4．5个月（RP型）；2例（RM450和RM453）的血浆病毒载量被控制至低于检测水平（Ec型）；其余13例属于NP型。与13只NP型的猴相比较，RM449（RP型）病毒载量高，SIV特异IgG低，效应记忆型CD4’T亚群细胞数低，且流式图出现类似“分化阻滞”的现象；外周血B细胞数的降幅大，以组织样B细胞和活化的记忆B细胞为主；淋巴组织耗竭，胸腺消失；具更高的抗淋巴组织的自身抗体的水平。而RM450和RM453猴（EC型）大致与之相反。结论AIDS的形成可能与T、B淋巴细胞亚群的分化和功能不足有关；而胸腺、淋巴组织等的结构破坏，可能是其病理学基础。Objective To compare the bio-medical parameters in SIV infected Chinese rhesus monkeys with diverse disease progression, by which the pathogenesis of simian AIDS were to be investigated. Methods Sixteen Chinese rhesus monkeys were inoculated intravenously with SIVmac239 and followed-up for 18 months. Based on their progression patterns and plasma viral loads, animals were divided into 3 groups, including 1 rapid progressor（ RP）, 13 normal progressors（ NP）, and 2 elite controllor（EC）. Their parameters of haematology, virology, immunology and pathology were examined and compared. Results Compared with other animals, RM449（RP） showed higher viral load, unresponsive humoral immunity, and higher level of auto-antibodies against lymph node, thymus, and spleen. Additionally, its effector memory CD4 count was lower, with the transformation progress being ＂blocked-like＂ from naive/central memory sub- sets to effector memory subset, as the flow-cytometry assay showed. Notable decrease in its peripheral B cell was also observed, especially to the sub-population of tissue-like memory B cells and activated memory B cells. Pathological examination showed the depletion of lymphoid tissue, atrophy of spleen and loss of thy- mus. Moreover, most of these parameters of RM450 and RM453 （EC） changed opposite to that of RP. Conclusion The hallmarks of RM449 were higher viraemia and lower SIV specific IgG level, which may due to the disturbance of T cells and B cells development and differentiation. Moreover, destructions of or- gans of the immune system may contribute to the disturbance. Our study suggest that the change of micro-en- vironments of thymus induced by SIV infection, which is necessary in T cell and B cell development and dif- ferentiation, may contribute at least partially to the AIDS pathogenesis.

关 键 词：快速进展型 一般进展型 精英控制者 猴免疫缺陷病毒 记忆细胞亚群 

分 类 号：R51[医药卫生—内科学]