Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing.
Cell. 2016-03-01; 165(1): 100-110
DOI: 10.1016/j.cell.2016.01.021
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1. Cell. 2016 Mar 24;165(1):100-110. doi: 10.1016/j.cell.2016.01.021. Epub 2016 Feb
25.
Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing.
Basu R(1), Whitlock BM(2), Husson J(3), Le Floc’h A(1), Jin W(4), Oyler-Yaniv
A(5), Dotiwala F(6), Giannone G(7), Hivroz C(8), Biais N(9), Lieberman J(6), Kam
LC(4), Huse M(10).
Author information:
(1)Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY
10065, USA.
(2)Biochemistry and Molecular Biology Graduate Program, Weill-Cornell Medical
College, New York, NY 10065, USA.
(3)Hydrodynamics Laboratory (LadHyX), Department of Mechanics, Ecole
Polytechnique, Palaiseau 91128, France.
(4)Department of Biomedical Engineering, Columbia University, New York, NY 10027,
USA.
(5)Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New
York, NY 10065, USA.
(6)Program in Cellular and Molecular Medicine, Harvard Medical School, Boston, MA
02115, USA.
(7)CNRS, University of Bordeaux, Interdisciplinary Institute for Neuroscience,
UMR 5297, Bordeaux 33000, France.
(8)Institute Curie, INSERM U932, PSL Research University, Paris 75005, France.
(9)Department of Biology, Brooklyn College of the City University of New York,
New York, NY 11201, USA.
(10)Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY
10065, USA. Electronic address: .
Comment in
Dev Cell. 2016 Mar 21;36(6):592-4.
The immunological synapse formed between a cytotoxic T lymphocyte (CTL) and an
infected or transformed target cell is a physically active structure capable of
exerting mechanical force. Here, we investigated whether synaptic forces promote
the destruction of target cells. CTLs kill by secreting toxic proteases and the
pore forming protein perforin into the synapse. Biophysical experiments revealed
a striking correlation between the magnitude of force exertion across the synapse
and the speed of perforin pore formation on the target cell, implying that force
potentiates cytotoxicity by enhancing perforin activity. Consistent with this
interpretation, we found that increasing target cell tension augmented pore
formation by perforin and killing by CTLs. Our data also indicate that CTLs
coordinate perforin release and force exertion in space and time. These results
reveal an unappreciated physical dimension to lymphocyte function and demonstrate
that cells use mechanical forces to control the activity of outgoing chemical
signals.
Copyright © 2016 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.cell.2016.01.021
PMCID: PMC4808403
PMID: 26924577 [Indexed for MEDLINE]