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Journal Articles Cell Year : 2016

Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing

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1
Roshni Basu
  • Function : Author
Benjamin m. Whitlock
  • Function : Author
Audrey Le floc’h
  • Function : Author
Weiyang Jin
  • Function : Author
Alon Oyler-Yaniv
  • Function : Author
Farokh Dotiwala
  • Function : Author
Gregory Giannone
Claire Hivroz
  • Function : Author
Nicolas Biais
  • Function : Author
Judy Lieberman
  • Function : Author
Lance c. Kam
  • Function : Author
Morgan Huse
  • Function : Author

Abstract

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.

Dates and versions

hal-01317871 , version 1 (18-05-2016)

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Roshni Basu, Benjamin m. Whitlock, Julien Husson, Audrey Le floc’h, Weiyang Jin, et al.. Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing. Cell, 2016, 165 (1), ⟨10.1016/j.cell.2016.01.021⟩. ⟨hal-01317871⟩
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