Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection
Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection
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DOI：
10.1073/pnas.93.26.15323
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发表时间：
1996-12-24
影响因子：
11.1
通讯作者：
Nowak, MA
中科院分区：
文献类型：
--
作者：
Klenerman, P;Phillips, RE;Nowak, MA
为了了解免疫系统在限制HIV 1型复制中的作用，关键是要知道在多大程度上，多产感染细胞的快速周转是由病毒细胞病变或免疫介导的裂解引起的。我们发现，许多患者未培养的外周血单个核细胞含有细胞毒性T淋巴细胞（CTL），它们以合理的外周血单个核细胞与靶标的比率裂解靶细胞，半衰期小于1天。在23例CD4计数为10 - 900 /亩的患者中，ctl介导的裂解平均速率对应于0.7天的靶细胞半衰期。我们开发了数学模型来计算受免疫介导的裂解和病毒细胞病变感染细胞的周转率，并估计被CTL杀死的细胞比例。这些模型为药物治疗动力学提供了新的解释，并解释了为什么观察到的病毒下降率对不同的患者大致是恒定的。我们得出结论，在HIV 1型感染中，ctl介导的裂解可以通过限制病毒产生来减少病毒载量，对感染细胞的半衰期影响很小。
To understand the role of the immune system in limiting HIV type 1 replication, it is critical to know to what extent the rapid turnover of productively infected cells is caused by viral cytopathicity or by immune-mediated lysis. We show that uncultured peripheral blood mononuclear cells of many patients contain cytotoxic T lymphocytes (CTL) that lyse target cells--at plausible peripheral blood mononuclear cell-to-target ratios--with half-lives of less than 1 day. In 23 patients with CD4 counts ranging from 10 to 900 per mu, the average rate of CTL-mediated lysis corresponds to a target cell half-life of 0.7 day. We develop mathematical models to calculate the turnover rate of infected cells subjected to immune-mediated lysis and viral cytopathicity and to estimate the fraction of cells that are killed by CTL as opposed to virus. The models provide new interpretations of drug treatment dynamics and explain why the observed rate of virus decline is roughly constant for different patients. We conclude that in HIV type 1 infection, CTL-mediated lysis can reduce virus load by limiting virus production, with small effects on the half-life of infected cells.