title: Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing.
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.
authors.affiliation: 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.
authors.forename: Zilton
authors.initials: Z
authors.lastname: Vasconcelos
authors.affiliation: 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.
authors.forename: Sabina
authors.initials: S
authors.lastname: Müller
authors.affiliation: 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.
authors.forename: Delphine
authors.initials: D
authors.lastname: Guipouy
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Wong
authors.initials: W
authors.lastname: Yu
authors.affiliation: Université Toulouse III Paul-Sabatier, 31062 Toulouse, France; Institut de Mathématiques de Toulouse, UMR 5219, 31062 Toulouse, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Christophe
authors.affiliation: Toulouse School of Economics, Université Toulouse I Capitole, 31000 Toulouse, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gadat
authors.affiliation: 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.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
authors.affiliation: 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.
authors.forename: Loïc
authors.initials: L
authors.lastname: Dupré
mesh_terms: D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D008962:Models, Theoretical; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*