艾滋病靈長類動物模型對于艾滋病發(fā)病機制研究、抗艾滋病藥物和疫苗的評價具有十分重要的意義,。迄今應(yīng)用最為廣泛的艾滋病靈長類動物模型是SIVmac或SHIV感染的印度恒河猴模型,。已有研究表明中國恒河猴是較印度恒河猴更為適合的艾滋病模型靈長類動物，SIV感染中國恒河猴的疾病進(jìn)程較為緩慢,，更為接近人艾滋病的發(fā)病進(jìn)程,。
艾滋病毒感染早期機體的免疫活化是導(dǎo)致疾病進(jìn)展快慢的一個主要原因。機體針對病毒所產(chǎn)生的免疫活化在清除病毒的同時也活化了HIV的靶細(xì)胞,，活化產(chǎn)生的炎癥因子還將導(dǎo)致免疫細(xì)胞的凋亡以及粘膜屏障的損傷,。樹突狀細(xì)胞DC作為最重要的連接先天免疫與獲得性免疫的抗原遞呈細(xì)胞，在艾滋病發(fā)病進(jìn)程中扮演著重要的角色,。
中國科學(xué)院昆明動物所動物模型與人類疾病機理重點實驗室的夏厚軍博士生等人在導(dǎo)師鄭永唐研究員的指導(dǎo)下,，對SIVmac239感染中國恒河猴后樹突狀細(xì)胞亞群的數(shù)量、表型和功能變化及其機制進(jìn)行了研究,。結(jié)果發(fā)現(xiàn),，與印度恒河猴感染時pDC被大量剔除，并始終處于低谷的情況不同,，SIV感染中國恒河猴時的pDC盡管在2周左右會明顯降低,，在感染后期則會逐漸恢復(fù)到正常范圍，而pDC分泌IFN-α的能力在急性感染期會顯著提高,，而在慢性期恢復(fù)到正常范圍,，進(jìn)入艾滋病期后則會急速降低。體外pDC分泌IFN-α的濃度與CD4 T細(xì)胞數(shù)量呈正相關(guān),，而與病毒載量呈負(fù)相關(guān),。另一DC亞群髓樣樹突狀細(xì)胞（mDC）的數(shù)量在感染過程并沒有顯著的改變，不過mDC分泌IL-12的能力在急性感染期顯著提高,，并伴隨著IFN-α的升高,。在整個感染過程中，pDC分泌IFN-α的濃度與mDC分泌IL-12的濃度呈顯著正相關(guān),，這表明IFN-α很可能激發(fā)了mDC成熟并分泌IL-12,。IFN-α在整個疾病進(jìn)展中發(fā)揮了雙重的作用，感染早期高水平的IFN-α會加速疾病的進(jìn)展，但在慢性感染期中度水平的IFN-α有利于延緩疾病的進(jìn)展,，該研究結(jié)果表明IFN-α在艾滋病發(fā)病進(jìn)程中發(fā)揮了十分重要的作用,，同時也可能作為艾滋病疾病進(jìn)程的指標(biāo)之一為臨床治療提供參考。
以上研究結(jié)果發(fā)表于《逆轉(zhuǎn)錄病毒學(xué)》（Retrovirology 2010, 7:102）,。相關(guān)研究獲國家自然科學(xué)基金,、中科院知識創(chuàng)新工程重要方向、國家科技重大專項“十一五”計劃課題的資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
