Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs

Immunity. 2007 Jun;26(6):798-811. doi: 10.1016/j.immuni.2007.04.010. Epub 2007 May 31.


Although activated murine NK cells can use the granule exocytosis pathway to kill target cells immediately upon recognition, resting murine NK cells are minimally cytotoxic for unknown reasons. Here, we showed that resting NK cells contained abundant granzyme A, but little granzyme B or perforin; in contrast, the mRNAs for all three genes were abundant. Cytokine-induced in vitro activation of NK cells resulted in potent cytotoxicity associated with a dramatic increase in granzyme B and perforin, but only minimal changes in mRNA abundance for these genes. The same pattern of regulation was found in vivo with murine cytomegalovirus infection as a physiologic model of NK cell activation. These data suggest that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / pharmacology
  • Cytomegalovirus Infections / immunology
  • Cytotoxicity, Immunologic* / genetics
  • Granzymes / analysis
  • Granzymes / genetics
  • Granzymes / metabolism*
  • Interleukin-15 / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Mutant Strains
  • Perforin
  • Pore Forming Cytotoxic Proteins / analysis
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / metabolism*
  • Protein Biosynthesis*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Secretory Vesicles / metabolism


  • Cytokines
  • Interleukin-15
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • perforin 1, mouse
  • Perforin
  • Granzymes

Associated data

  • GEO/GSE7764