Delivering the kiss of death

Nat Immunol. 2003 May;4(5):399-403. doi: 10.1038/ni0503-399.


Cytotoxic T lymphocytes and natural killer cells kill their targets by secreting specialized granules that contain potent cytotoxic molecules. Through the study of rare immunodeficiency diseases in which this granule pathway of killing is impaired, proteins such as Rab27a have been identified as components of the secretory machinery of these killer cells. Recent evidence suggests that the destruction of activated lymphocytes through granule-mediated killing may be an important mechanism of immunological homeostasis. Although the process by which this occurs is not yet known, it is possible that events taking place at the immunological synapse may render the killer cell susceptible to fratricidal attack by other killer cells.

Publication types

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

MeSH terms

  • Animals
  • Chediak-Higashi Syndrome / genetics
  • Chediak-Higashi Syndrome / immunology
  • Cytoplasmic Granules / immunology
  • Cytotoxicity, Immunologic / genetics
  • Hermanski-Pudlak Syndrome / genetics
  • Hermanski-Pudlak Syndrome / immunology
  • Histiocytosis, Non-Langerhans-Cell / genetics
  • Histiocytosis, Non-Langerhans-Cell / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Mice
  • Mutation
  • T-Lymphocytes, Cytotoxic / immunology*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / immunology
  • rab27 GTP-Binding Proteins


  • rab27 GTP-Binding Proteins
  • RAB27A protein, human
  • Rab27a protein, mouse
  • rab GTP-Binding Proteins