Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.
PLoS One. 2011 Jan 24;6(1):e15959. doi: 10.1371/journal.pone.0015959.
It has been difficult to correlate the quality of CD8 T cell responses with protection against viral infections. To investigate the relationship between efficacy and magnitude of T cell responses, we quantify the rate at which individual CD8 effector and memory T cells kill target cells in the mouse spleen. Using mathematical modeling, we analyze recent data on the loss of target cells pulsed with three different peptides from the mouse lymphocytic choriomeningitis virus (LCMV) in mouse spleens with varying numbers of epitope-specific CD8 T cells. We find that the killing of targets follows the law of mass-action, i.e., the death rate of individual target cells remains proportional to the frequency (or the total number) of specific CD8 T cells in the spleen despite the fact that effector cell densities and effector to target ratios vary about a 1000-fold. The killing rate of LCMV-specific CD8 T cells is largely independent of T cell specificity and differentiation stage. Our results thus allow one to calculate the critical T cell concentration at which growth of a virus with a given replication rate can be prevented from the start of infection by memory CD8 T cell response.
将 CD8 T 细胞应答的质量与针对病毒感染的保护相关联一直存在困难。为了研究 T 细胞应答的功效和幅度之间的关系，我们定量测定了个体 CD8 效应和记忆 T 细胞在小鼠脾脏中杀死靶细胞的速度。我们使用数学模型，分析了最近关于在具有不同数量的针对三种不同的来自小鼠淋巴细胞性脉络丛脑膜炎病毒（LCMV）的肽的特异性 CD8 T 细胞的小鼠脾脏中，用脉冲处理的靶细胞丢失的实验数据。我们发现，靶细胞的杀伤遵循质量作用定律，即尽管效应细胞密度和效应物与靶物的比率变化约 1000 倍，但个体靶细胞的死亡率仍与脾脏中特异性 CD8 T 细胞的频率（或总数）成比例。LCMV 特异性 CD8 T 细胞的杀伤率在很大程度上与 T 细胞特异性和分化阶段无关。因此，我们的结果使得人们可以根据给定的复制率，从感染开始时，计算出防止具有特定复制率的病毒生长所需的临界 T 细胞浓度，这取决于记忆 CD8 T 细胞的应答。
