Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
PLoS Pathog. 2010 Jan 29;6(1):e1000748. doi: 10.1371/journal.ppat.1000748.
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.
CD8+ T 细胞是抗病毒免疫的关键介质,通过先天和适应性机制,可能有助于控制致病性慢病毒感染。我们研究了在抗逆转录病毒治疗感染猴免疫缺陷病毒(SIV)的恒河猴时 CD8+ T 细胞耗竭后病毒动力学,以测试适应性细胞毒性效应对清除 SIV 感染的细胞的重要性。如前所述,CD8+ T 细胞耗竭后血浆病毒载量(VL)增加,与 GALT 中 CD8+ T 细胞耗竭的程度成正比,证实了 CD8+ T 细胞丢失与病毒复制之间的直接关系。令人惊讶的是,与对照组相比,CD8+ T 细胞耗竭动物在给予抗逆转录病毒药物后的第一相血浆病毒衰减并不慢,这表明平均感染细胞的短暂寿命并不是细胞毒性 T 淋巴细胞(CTL)杀伤的反映。我们的发现支持 CD8+ T 细胞对控制致病性慢病毒感染的非细胞毒性效应的主导作用,并表明如果存在细胞毒性效应,也仅限于病毒生命周期的早期、前生产阶段。这些观察结果对增强 HIV 免疫控制的未来策略具有重要意义。