Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection.
Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection.
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DOI：
10.1371/journal.ppat.1000295
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发表时间：
2009-02
期刊：
影响因子：
6.7
通讯作者：
McCune JM
中科院分区：
文献类型：
--
作者：
Favre D;Lederer S;Kanwar B;Ma ZM;Proll S;Kasakow Z;Mold J;Swainson L;Barbour JD;Baskin CR;Palermo R;Pandrea I;Miller CJ;Katze MG;McCune JM
慢性免疫激活和艾滋病的进展后，SIV感染猕猴，但不是在自然宿主灵长类动物物种。为了更好地理解这种二分法，我们比较了猪尾猕猴（PT）的急性致病性SIV感染和非洲绿色猴（AGM）的非致病性感染。SIVagm感染的PT，但不是SIVagm感染的AGM，迅速发展全身免疫激活，IL-17分泌（Th 17）细胞的显著和选择性耗竭，以及血液，淋巴器官和粘膜组织中Th 17和T调节（Treg）细胞之间的平衡丧失。Th 17细胞的丧失被认为是系统性和持续性T细胞活化的预测。总的来说，这些数据表明Th 17与Treg平衡的丧失与SIV疾病进展有关。猴免疫缺陷病毒（SIV）在40多种不同种类的非洲非人灵长类动物中的自然感染并不伴随着获得性免疫缺陷综合征（AIDS）的进展。为了理解这一现象，我们对两个不同物种的急性SIV感染进行了详细的病毒学、免疫学和基因表达分析：非洲绿色猴（AGM），其中SIV感染是非致病性的;亚洲小尾猕猴（PT），其中SIV感染导致AIDS。实验感染后，两个物种的动物都产生了高病毒载量。在PT中，病毒血症与外周血中的CD 4 + T细胞耗竭以及持续免疫激活和炎症的多种体征相关。在AGM中未观察到这种病理学。值得注意的是，AGM维持高水平和平衡的两个亚群的CD 4 + T细胞，例如，免疫抑制性T调节（Treg）和IL-17产生（Th 17）群体，而PT则没有。进一步分析Th 17和Treg平衡在致病性慢病毒感染过程中的作用可能为我们理解SIV和HIV的发病机制以及未来疫苗开发提供新的见解。
Chronic immune activation and progression to AIDS are observed after SIV infection in macaques but not in natural host primate species. To better understand this dichotomy, we compared acute pathogenic SIV infection in pigtailed macaques (PTs) to non-pathogenic infection in African green monkeys (AGMs). SIVagm-infected PTs, but not SIVagm-infected AGMs, rapidly developed systemic immune activation, marked and selective depletion of IL-17-secreting (Th17) cells, and loss of the balance between Th17 and T regulatory (Treg) cells in blood, lymphoid organs, and mucosal tissue. The loss of Th17 cells was found to be predictive of systemic and sustained T cell activation. Collectively, these data indicate that loss of the Th17 to Treg balance is related to SIV disease progression. Natural infection by the simian immunodeficiency virus (SIV) in over 40 different species of African non-human primates is not accompanied by progression to acquired immunodeficiency syndrome (AIDS). To understand this phenomenon, we have performed a detailed virologic, immunologic, and gene expression analysis of acute SIV infection of two disparate species: the African green monkey (AGM), in which SIV infection is nonpathogenic, and the Asian pigtailed macaque (PT), in which SIV infection results in AIDS. After experimental infection, animals of both species developed high viral loads. In the PTs, viremia was associated with CD4+ T cell depletion in the peripheral blood and multiple signs of persistent immune activation and inflammation. Such pathology was not observed in AGMs. Notably, the AGMs maintained high and balanced levels of two subset populations of CD4+ T cells, e.g., the immunosuppressive T regulatory (Treg) and the IL-17 producing (Th17) populations, whereas the PTs did not. Further analysis of the role of Th17 and Treg balance during pathogenic lentiviral infection may provide novel insights into our understanding of SIV and HIV pathogenesis and future thoughts about vaccine development.
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