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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein.
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Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein.

机译：猕猴增强了SIV复制并加速了向AIDS的进展，引发了对SIV包膜蛋白的CD4 T细胞应答。

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摘要

Given the dual role of CD4 T cells as both immune effectors and targets for HIV infection, the balance of CD4 versus CD8 T cell-mediated responses induced by candidate AIDS vaccines may be critical in determining postvaccination infection outcomes. An attenuated recombinant varicella-zoster virus vaccine expressing the simian immunodeficiency virus (SIV) envelope (Env) elicited nonneutralizing Env-binding antibodies and little if any cytotoxic T lymphocyte responses in rhesus macaques (Macaca mulatta). After challenge with SIV, Env vaccinees manifested increased levels of SIV replication, more rapid CD4 depletion, and accelerated progression to AIDS compared with controls. Enhanced SIV replication correlated with increased CD4 T cell proliferation soon after SIV challenge, apparently the result of an anamnestic response to SIV antigens. Thus activation of virus-specific CD4 T cells at the time of exposure to a CD4 T cell-tropic lentivirus, in the absence of an effective CD8 response, may enhance virus replication and disease. These data suggest suggest that candidate AIDS vaccines may not simply be either efficacious or neutral; they may also have the potential to be harmful.
机译：考虑到CD4 T细胞既是免疫效应物又是HIV感染目标的双重作用，候选AIDS疫苗诱导的CD4与CD8 T细胞介导的反应之间的平衡可能对确定疫苗接种后的感染结果至关重要。表达猿猴免疫缺陷病毒（SIV）包膜（Env）的减毒重组水痘带状疱疹病毒疫苗在恒河猴（猕猴）中引起非中和的Env结合抗体和极少的细胞毒性T淋巴细胞反应。与对照组相比，用SIV攻击后，Env疫苗表现出SIV复制水平增加，CD4消耗更快，并加速发展为AIDS。 SIV攻击后不久，增强的SIV复制与增加的CD4 T细胞增殖相关，这显然是对SIV抗原的记忆消除反应的结果。因此，在缺乏有效的CD8应答的情况下，暴露于CD4 T细胞嗜性慢病毒时，病毒特异性CD4 T细胞的活化可能会增强病毒复制和疾病。这些数据表明，候选艾滋病疫苗可能不只是有效的或中性的。它们也可能有害。

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