The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal

Nat Rev Immunol. 2003 May;3(5):361-70. doi: 10.1038/nri1083.


Granule exocytosis is the main pathway for the immune elimination of virus-infected cells and tumour cells by cytotoxic T lymphocytes and natural killer cells. After target-cell recognition, release of the cytotoxic granule contents into the immunological synapse formed between the killer cell and its target induces apoptosis. The granules contain two membrane-perturbing proteins, perforin and granulysin, and a family of serine proteases known as granzymes, complexed with the proteoglycan serglycin. In this review, I discuss recent insights into the mechanisms of granule-mediated cytotoxicity, focusing on how granzymes A, B and C and granulysin activate cell death through caspase-independent pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cytotoxicity, Immunologic*
  • Exocytosis
  • Granzymes
  • Mice
  • Models, Immunological
  • Secretory Vesicles / chemistry
  • Secretory Vesicles / enzymology*
  • Serine Endopeptidases / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology


  • Granzymes
  • Gzmb protein, mouse
  • Gzmc protein, mouse
  • Serine Endopeptidases