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Cell Rep. 2015 Jun 9;11(9):1474-85. doi: 10.1016/j.celrep.2015.05.002. Epub 2015 May 28.

Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing.

Author information

1
INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, 31300 Toulouse, France; Université Toulouse III Paul-Sabatier, 31062 Toulouse, France; CNRS, UMR 5282, 31300 Toulouse, France; Fernandes Figueira Institute, Fiocruz, 22250-020 Rio de Janeiro, Brazil.
2
INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, 31300 Toulouse, France; Université Toulouse III Paul-Sabatier, 31062 Toulouse, France; CNRS, UMR 5282, 31300 Toulouse, France.
3
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Université Toulouse III Paul-Sabatier, 31062 Toulouse, France; Institut de Mathématiques de Toulouse, UMR 5219, 31062 Toulouse, France.
5
Toulouse School of Economics, Université Toulouse I Capitole, 31000 Toulouse, France.
6
INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, 31300 Toulouse, France; Université Toulouse III Paul-Sabatier, 31062 Toulouse, France; CNRS, UMR 5282, 31300 Toulouse, France. Electronic address: salvatore.valitutti@inserm.fr.
7
INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, 31300 Toulouse, France; Université Toulouse III Paul-Sabatier, 31062 Toulouse, France; CNRS, UMR 5282, 31300 Toulouse, France. Electronic address: loic.dupre@inserm.fr.

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 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.

PMID:
26027932
DOI:
10.1016/j.celrep.2015.05.002
[Indexed for MEDLINE]
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