The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus
The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus
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DOI：
10.1182/blood-2005-12-4897
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发表时间：
2006-07-01
期刊：
影响因子：
20.3
通讯作者：
Silvestri, Guido
中科院分区：
文献类型：
--
作者：
Dunham, Richard;Pagliardini, Paola;Silvestri, Guido
与人类免疫缺陷病毒（HIV）感染的人类相比，猿猴免疫缺陷病毒（SIV）的自然宿主很少发展为获得性免疫缺陷综合症（AIDS）。虽然人们对这种疾病抵抗力的机制仍知之甚少，但自然 SIV 感染的一个一致特征是缺乏与 HIV 感染相关的全身免疫激活。为了研究自然宿主物种 SIV 感染的乌白眉猴 (SM) 中不存在 AIDS 的免疫机制，我们对 110 个 SIV 感染的 SM 中的 SIV 特异性细胞免疫反应进行了详细分析。我们发现，虽然在大多数动物中可以检测到 SIV 特异性 T 细胞反应，但事实上，无论是在细胞因子产生（即 IFN-γ、TNF-α 和 IL-2）还是脱颗粒（即 CD107a 表达）方面，其幅度和广度均低于 HIV 感染人类中所描述的水平和广度。重要的是，当使用 SIVmac239 衍生肽或自体 SIVsmm 肽作为刺激物时，SIV 特异性 T 细胞反应同样较低。在SIV特异性T细胞反应与病毒载量或CD4(+) T细胞计数之间，或者这些反应与T细胞活化和增殖标志物之间没有发现相关性。这些发现表明，自然感染 SIV 的乌白白眉猴中不存在艾滋病，与对该病毒的强烈细胞免疫反应无关。
In contrast to human immunodeficiency virus (HIV)-infected humans, natural hosts for simian immunodeficiency virus (SIV) very rarely progress to acquired immunodeficiency syndrome (AIDS). While the mechanisms underlying this disease resistance are still poorly understood, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To investigate the immunologic mechanisms underlying the absence of AIDS in SIV-infected sooty mangabeys (SMs), a natural host species, we performed a detailed analysis of the SIV-specific cellular immune responses in 110 SIV-infected SMs. We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIV-infected humans, both in terms of cytokine production (ie, IFN-gamma, TNF-alpha, and IL-2) and degranulation (le, CD107a expression). Of importance, SIV-specific T-cell responses were similarly low when either SIVmac239-derived peptides or autologous SIVsmm peptides were used as stimuli. No correlation was found between SIV-specific T-cell responses and either viral load or CD4(+) T-cell count, or between these responses and markers of T-cell activation and proliferation. These findings indicate that the absence of AIDS in naturally SIV-infected sooty mangabeys is independent of a strong cellular immune response to the virus.