Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells

Cell. 1994 Mar 25;76(6):977-87. doi: 10.1016/0092-8674(94)90376-x.


We have generated H-2b mice with a homozygous null mutation in the granzyme (gzm) B gene. Gzm B is a neutral serine protease with Aspase activity that is found only in the granules of activated cytolytic T cells, natural killer cells, and lymphokine-activated killer cells. Gzm B-/- mice develop normally and have normal hematopoiesis and lymphopoiesis. In vitro, cytotoxic T lymphocytes (CTL) derived from gzm B-/- animals are able to induce 51Cr release from allotarget cells, but with reduced efficiency. However, gzm B-/- CTL have a profound defect in their ability to induce rapid DNA fragmentation and apoptosis in allogeneic target cells. This defect is kinetic since DNA fragmentation is partially compensated and 51Cr release is completely rescued with long incubation times. We conclude that gzm B serves a critical and nonredundant role for the rapid induction of target cell DNA fragmentation and apoptosis by alloreactive cytotoxic T lymphocytes.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • DNA / metabolism*
  • Embryo, Mammalian / cytology
  • Granzymes
  • Hematopoiesis / physiology
  • Killer Cells, Natural / enzymology
  • Killer Cells, Natural / physiology*
  • Lymphocyte Activation / physiology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Multigene Family
  • Mutation
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Stem Cells
  • T-Lymphocytes, Cytotoxic / enzymology
  • T-Lymphocytes, Cytotoxic / physiology*


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