The Role of Granzyme B Cluster Proteases in Cell-Mediated Cytotoxicity

Semin Immunol. 1997 Apr;9(2):127-33. doi: 10.1006/smim.1997.0060.

Abstract

Granzymes are neutral serine proteases that are stored in the specialized lytic granules of cytotoxic lymphocytes. A mutation introduced into the granzyme B locus leads to a severe defect in the ability of cytotoxic lymphocytes to induce apoptosis in susceptible target cells, and reduces the severity of class I-dependent acute graft-versus-host disease (GvHD). However, granzyme B-independent cytotoxicity also exists: in CD8+ cells, most of it is perforin-dependent, but in CD4+ cells, the Fas system and an additional pathway are involved. The identification of these pathways and their physiological relevance may lead to new approaches for inhibiting cytotoxic lymphocyte functions.

Publication types

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

MeSH terms

  • Animals
  • Caspase 1
  • Chromosome Mapping
  • Cysteine Endopeptidases / metabolism
  • Cytotoxicity, Immunologic*
  • Enzyme Activation
  • Exocytosis
  • Gene Expression
  • Gene Expression Regulation, Enzymologic
  • Graft vs Host Disease / immunology
  • Granzymes
  • Humans
  • Immunity, Cellular
  • Serine Endopeptidases / physiology*
  • T-Lymphocytes, Cytotoxic / enzymology*

Substances

  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • Cysteine Endopeptidases
  • Caspase 1