The kinematics of cytotoxic lymphocytes influence their ability to kill target cells

Bhat, Purnima, Leggatt, Graham, Matthaei, Klaus I. and Frazer, Ian H. (2014) The kinematics of cytotoxic lymphocytes influence their ability to kill target cells. PLoS One, 9 5: e95248.1-e95248.11. doi:10.1371/journal.pone.0095248


Author Bhat, Purnima
Leggatt, Graham
Matthaei, Klaus I.
Frazer, Ian H.
Title The kinematics of cytotoxic lymphocytes influence their ability to kill target cells
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-05-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0095248
Open Access Status DOI
Volume 9
Issue 5
Start page e95248.1
End page e95248.11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2015
Language eng
Abstract Cytotoxic lymphocytes (CTL) have been reported to show a range of motility patterns from rapid long-range tracking to complete arrest, but how and whether these kinematics affect their ability to kill target cells is not known. Many in vitro killing assays utilize cell lines and tumour-derived cells as targets, which may be of limited relevance to the kinetics of CTL-mediated killing of somatic cells. Here, live-cell microscopy is used to examine the interactions of CTL and primary murine skin cells presenting antigens. We developed a qualitative and quantitative killing assay using extended-duration fluorescence time-lapse microscopy coupled with large-volume objective software-based data analysis to obtain population data of cell-to-cell interactions, motility and apoptosis. In vivo and ex vivo activated antigen-specific cytotoxic lymphocytes were added to primary keratinocyte targets in culture with fluorometric detection of caspase-3 activation in targets as an objective determinant of apoptosis. We found that activated CTL achieved contact-dependent apoptosis of non-tumour targets after a period of prolonged attachment - on average 21 hours - which was determined by target cell type, amount of antigen, and activation status of CTL. Activation of CTL even without engagement of the T cell receptor was sufficient to mobilise cells significantly above baseline, while the addition of cognate antigen further enhanced their motility. Highly activated CTL showed markedly increased vector displacement, and velocity, and lead to increased antigen-specific target cell death. These data show that the inherent kinematics of CTL correlate directly with their ability to kill non-tumour cells presenting cognate antigen.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 20 May 2014, 07:09:28 EST by Dr Graham Leggatt on behalf of UQ Diamantina Institute