The role of granzyme B cluster proteases in cell-mediated cytotoxicity.
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.
Pham
C T
CT
Department of Internal Medicine and Genetics, Washington University Medical School, St Louis, MO 63110-1093, USA.
Ley
T J
TJ
D000818:Animals; D020170:Caspase 1; D002874:Chromosome Mapping; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D005089:Exocytosis; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D006086:Graft vs Host Disease / Q000276:immunology; D053804:Granzymes; D006801:Humans; D007111:Immunity, Cellular; D012697:Serine Endopeptidases / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*
C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D020170:Caspase 1