Delivering the kiss of death: progress on understanding how perforin works

Curr Opin Immunol. 2007 Jun;19(3):301-8. doi: 10.1016/j.coi.2007.04.011. Epub 2007 Apr 12.


Killer lymphocytes release perforin and granzymes from cytotoxic granules into the immunological synapse to destroy target cells as a critical mechanism in the defense against viruses and cancer. Perforin, a Ca(2+)-dependent pore-forming protein that multimerizes in membranes, delivers granzymes into the target cell cytosol. The original model for perforin (acting by forming a cell membrane channel through which granzymes pass) does not fit the experimental data. Recently, an alternative model has been proposed that involves active target cell collaboration with perforin to deliver granzymes and direct the target cell to an apoptotic, rather than necrotic, death.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic*
  • Granzymes / immunology
  • Granzymes / metabolism
  • Humans
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Models, Immunological*
  • Perforin
  • Pore Forming Cytotoxic Proteins / immunology*
  • Pore Forming Cytotoxic Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Granzymes