艾滋病灵长类动物模型对于艾滋病发病机制研究、抗艾滋病药物和疫苗的评价具有十分重要的意义。迄今应用最为广泛的艾滋病灵长类动物模型是SIVmac或SHIV感染的印度恒河猴模型。已有研究表明中国恒河猴是较印度恒河猴更为适合的艾滋病模型灵长类动物，SIV感染中国恒河猴的疾病进程较为缓慢，更为接近人艾滋病的发病进程。
艾滋病毒感染早期机体的免疫活化是导致疾病进展快慢的一个主要原因。机体针对病毒所产生的免疫活化在清除病毒的同时也活化了HIV的靶细胞，活化产生的炎症因子还将导致免疫细胞的凋亡以及粘膜屏障的损伤。树突状细胞DC作为最重要的连接先天免疫与获得性免疫的抗原递呈细胞，在艾滋病发病进程中扮演着重要的角色。
中国科学院昆明动物所动物模型与人类疾病机理重点实验室的夏厚军博士生等人在导师郑永唐研究员的指导下，对SIVmac239感染中国恒河猴后树突状细胞亚群的数量、表型和功能变化及其机制进行了研究。结果发现，与印度恒河猴感染时pDC被大量剔除，并始终处于低谷的情况不同，SIV感染中国恒河猴时的pDC尽管在2周左右会明显降低，在感染后期则会逐渐恢复到正常范围，而pDC分泌IFN-α的能力在急性感染期会显著提高，而在慢性期恢复到正常范围，进入艾滋病期后则会急速降低。体外pDC分泌IFN-α的浓度与CD4 T细胞数量呈正相关，而与病毒载量呈负相关。另一DC亚群髓样树突状细胞（mDC）的数量在感染过程并没有显著的改变，不过mDC分泌IL-12的能力在急性感染期显著提高，并伴随着IFN-α的升高。在整个感染过程中，pDC分泌IFN-α的浓度与mDC分泌IL-12的浓度呈显著正相关，这表明IFN-α很可能激发了mDC成熟并分泌IL-12。IFN-α在整个疾病进展中发挥了双重的作用，感染早期高水平的IFN-α会加速疾病的进展，但在慢性感染期中度水平的IFN-α有利于延缓疾病的进展，该研究结果表明IFN-α在艾滋病发病进程中发挥了十分重要的作用，同时也可能作为艾滋病疾病进程的指标之一为临床治疗提供参考。
以上研究结果发表于《逆转录病毒学》（Retrovirology 2010, 7:102）。相关研究获国家自然科学基金、中科院知识创新工程重要方向、国家科技重大专项“十一五”计划课题的资助。（生物谷Bioon.com）
生物谷推荐原文出处：
Retrovirology doi:10.1186/1742-4690-7-102
Dendritic cell subsets dynamics and cytokine production in SIVmac239-infected Chinese rhesus macaques
Hou-Jun Xia , Gao-Hong Zhang , Jian-Ping Ma , Zheng-Xi Dai , Shao-You Li , Jian-Bao Han and Yong-Tang Zheng
Abstract (provisional)
Background
Several studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs.
Results
The numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-alpha significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-alpha emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-alpha may initiate the immune activation. We also found that only the concentration of IFN-alpha was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load.
Conclusion
High levels of IFN-alpha in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-alpha during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness.
