Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing.
Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing.
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DOI：
10.1016/j.celrep.2015.05.002
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发表时间：
2015-06
期刊：
影响因子：
8.8
通讯作者：
Z. Vasconcelos;S. Müller;Delphine Guipouy;Wong Yu;Claire Christophe;S. Gadat;S. Valitutti;L. Dupré
中科院分区：
文献类型：
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作者：
Z. Vasconcelos;S. Müller;Delphine Guipouy;Wong Yu;Claire Christophe;S. Gadat;S. Valitutti;L. Dupré
细胞毒性T淋巴细胞（CTL）的克隆群体对携带抗原的细胞的杀伤被认为是由单个CTL均匀执行的快速现象。我们在一个延长的时间段内结合了大量和单CTL杀伤测定，以提供克隆人CTL对过量靶细胞的杀伤统计数据。我们的数据揭示了在种群水平上持续杀伤的效率，这依赖于在个体水平上高度异质的多重杀伤性能。尽管克隆内功能异质性在克隆群体中是一个稳定的性状，但它在单个CTL的后代中被重置。对单个CTL杀伤数据的深入数学分析揭示了具有爆发杀伤活性的高速率杀伤CTL的相当大的比例。重要的是，这种活性被延迟，需要用强抗原刺激激活。我们的研究表明，功能异质性允许CTL群体校准延长的细胞毒活性的大小的靶细胞群体。
The killing of antigen-bearing cells by clonal populations of cytotoxic T lymphocytes (CTLs) is thought to be a rapid phenomenon executed uniformly by individual CTLs. We combined bulk and single-CTL killing assays over a prolonged time period to provide the killing statistics of clonal human CTLs against an excess of target cells. Our data reveal efficiency in sustained killing at the population level, which relied on a highly heterogeneous multiple killing performance at the individual level. Although intraclonal functional heterogeneity was a stable trait in clonal populations, it was reset in the progeny of individual CTLs. In-depth mathematical analysis of individual CTL killing data revealed a substantial proportion of high-rate killer CTLs with burst killing activity. Importantly, such activity was delayed and required activation with strong antigenic stimulation. Our study implies that functional heterogeneity allows CTL populations to calibrate prolonged cytotoxic activity to the size of target cell populations.