Cell Reports
Volume 11, Issue 9, 9 June 2015, Pages 1474-1485
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Article
Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing

https://doi.org/10.1016/j.celrep.2015.05.002Get rights and content
Under a Creative Commons license
open access

Highlights

  • Sustained killing activity allows CTLs to control an excess of target cells

  • The multiple killing performance of individual CTLs is highly heterogeneous

  • High-rate killing is delayed in time and requires strong antigenic stimulation

Summary

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.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Co-senior author