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.

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.

Available Versions of this Item

• Individual human cytotoxic T Lymphocytes exhibit intraclonal heterogeneity in cumulative killing. (deposited 16 Mar 2015 14:52)
  • Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing. (deposited 05 Nov 2015 15:10) [Currently Displayed]