Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Pathog. 2010 Jan 29;6(1):e1000747. doi: 10.1371/journal.ppat.1000747.
While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.
虽然 CD8+ T 细胞在控制 HIV 和 SIV 感染期间的病毒复制方面显然很重要，但这种抗病毒作用的机制仍知之甚少。在这项研究中，我们评估了 CD8+ 淋巴细胞耗竭对慢性 SIVmac239 感染恒河猴体内感染细胞寿命的体内影响。我们用抗逆转录病毒疗法治疗了两组动物，一组是 CD8+ 淋巴细胞耗竭组，另一组是对照组，并使用数学模型来评估有或没有 CD8+ 淋巴细胞存在时感染细胞的寿命。我们发现，在早期（感染 SIV 后第 57 天）和晚期（感染 SIV 后第 177 天）慢性 SIV 感染中，CD8+ 淋巴细胞耗竭均未导致体内短寿命或长寿命的感染细胞寿命明显延长。这一结果表明，CD8+ 淋巴细胞的存在并不会导致感染 SIV 的细胞寿命明显缩短，因此，直接细胞杀伤不太可能是 CD8+ T 细胞在高病毒复制的 SIV 感染猕猴中发挥抗病毒作用的主要机制。
