Functional significance of the perforin/granzyme cell death pathway

Nat Rev Immunol. 2002 Oct;2(10):735-47. doi: 10.1038/nri911.


Perforin/granzyme-induced apoptosis is the main pathway used by cytotoxic lymphocytes to eliminate virus-infected or transformed cells. Studies in gene-disrupted mice indicate that perforin is vital for cytotoxic effector function; it has an indispensable, but undefined, role in granzyme-mediated apoptosis. Despite its vital importance, the molecular and cellular functions of perforin and the basis of perforin and granzyme synergy remain poorly understood. The purpose of this review is to evaluate critically recent findings on cytotoxic granule-mediated cell death and to assess the functional significance of postulated cell-death pathways in appropriate pathophysiological contexts, including virus infection and susceptibility to experimental or spontaneous tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology*
  • Apoptosis / physiology
  • Autoimmunity
  • Graft vs Host Disease / etiology
  • Histiocytosis, Non-Langerhans-Cell / etiology
  • Humans
  • Infections / etiology
  • Killer Cells, Natural / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Mutant Strains
  • Models, Immunological
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / physiology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Serine Endopeptidases