Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing

Christophe, Claire, Dupré, Loïc, Gadat, Sébastien, Guipouy, Delphine, Müller, Sabina, Valitutti, Salvatore, Vasconcelos, Zilton and Yu, Wong (2015) Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing. Cell Reports, 11 (9). pp. 1474-1485.

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Official URL: http://tse-fr.eu/pub/29828

Abstract

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 pro-vide 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 pro-portion 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 al-lows CTL populations to calibrate prolonged cytotoxic activity to the size of target cell populations.

Item Type: Article
Language: English
Date: 9 June 2015
Refereed: Yes
Subjects: B- ECONOMIE ET FINANCE
Divisions: TSE-R (Toulouse)
Site: UT1
Date Deposited: 05 Nov 2015 15:10
Last Modified: 07 Mar 2018 13:23
OAI ID: oai:tse-fr.eu:29828
URI: http://publications.ut-capitole.fr/id/eprint/18600

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