Lymphocyte-mediated cytotoxicity.
Virtually all of the measurable cell-mediated cytotoxicity delivered by cytotoxic T lymphocytes and natural killer cells comes from either the granule exocytosis pathway or the Fas pathway. The granule exocytosis pathway utilizes perforin to traffic the granzymes to appropriate locations in target cells, where they cleave critical substrates that initiate DNA fragmentation and apoptosis; granzymes A and B induce death via alternate, nonoverlapping pathways. The Fas/FasL system is responsible for activation-induced cell death but also plays an important role in lymphocyte-mediated killing under certain circumstances. The interplay between these two cytotoxic systems provides opportunities for therapeutic interventions to control autoimmune diseases and graft vs. host disease, but oversuppression of these pathways may also lead to increased viral susceptibility and/or decreased tumor cell killing.
Russell
John H
JH
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. jrussell@pcg.wustl.edu
Ley
Timothy J
TJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005089:Exocytosis; D053200:Fas-Associated Death Domain Protein; D006087:Graft vs Host Reaction / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D053804:Granzymes; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000276:immunology; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C509212:GZMA protein, human