PDF(Pubmed)
Abstract：
Whether CD8+ T lymphocytes control human immunodeficiency virus infection by cytopathic or non-cytopathic mechanisms is not fully understood. Multiple studies highlighted non-cytopathic effects, but one hypothesis is that cytopathic effects of CD8+ T cells occur before viral production. Here, to examine the role of CD8+ T cells prior to virus production, we treated SIVmac251-infected macaques with an integrase inhibitor combined with a CD8-depleting antibody, or with either reagent alone. We analyzed the ensuing viral dynamics using a mathematical model that included infected cells pre- and post- viral DNA integration to compare different immune effector mechanisms. Macaques receiving the integrase inhibitor alone experienced greater viral load decays, reaching lower nadirs on treatment, than those treated also with the CD8-depleting antibody. Models including CD8+ cell-mediated reduction of viral production (non-cytolytic) were found to best explain the viral profiles across all macaques, in addition an effect in killing infected cells pre-integration (cytolytic) was supported in some of the best models. Our results suggest that CD8+ T cells have both a cytolytic effect on infected cells before viral integration, and a direct, non-cytolytic effect by suppressing viral production.
摘要：
尚不完全了解CD8T淋巴细胞是否通过细胞病变或非细胞病变机制控制人类免疫缺陷病毒感染。多项研究强调了非细胞病变效应，但一个假设是CD8+T细胞的细胞病变效应发生在病毒产生之前。这里,为了在病毒产生之前检查CD8+T细胞的作用，我们用整合酶抑制剂联合CD8消耗抗体治疗SIVmac251感染的猕猴，或者单独使用任何一种试剂。我们使用包括病毒DNA整合前和后感染细胞的数学模型分析了随后的病毒动力学，以比较不同的免疫效应机制。单独接受整合酶抑制剂的猕猴经历了更大的病毒载量衰减，在治疗中达到较低的最低点，比那些也用CD8消耗抗体治疗。包括CD8+细胞介导的减少病毒生产（非细胞溶解性）的模型被发现最好地解释了所有猕猴的病毒谱，此外,在一些最佳模型中支持了在预整合(溶细胞性)中杀死感染细胞的作用.我们的结果表明，CD8+T细胞在病毒整合之前对感染细胞有细胞溶解作用，和一个直接的，通过抑制病毒产生的非细胞溶解作用。
