Cell-mediated cytotoxicity: contact and secreted factors.
The list of cells with cytotoxic potential now may include small resting T cells, but the exact nature of 'lethal hit delivery' by cytotoxic T lymphocytes remains elusive. Cell-mediated cytotoxicity by cytotoxic T lymphocytes is a complex, multistep process which seems likely to be mediated by several different pathways. Recent experimental evidence for the functioning of a novel cytotoxic mechanism through a target cell's surface receptor illustrates and emphasizes the necessity to study the interactions of cytotoxic T lymphocytes and target cells as a whole. Progress is evident in the description of molecular requirements for triggering cytotoxicity, cell-cell contacts and the regulation of the effector responses of cytotoxic T lymphocytes by extracellular, intracellular and granular proteins. Extracellular Ca(2+)-dependent secretion of perforin and protease(s) may explain several aspects of cellular cytotoxicity, whereas the apoptosis-mediating cell surface Fas protein is now implicated in Ca(2+)-independent cytotoxicity.
Apasov
S
S
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Redegeld
F
F
Sitkovsky
M
M
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D004249:DNA Damage; D005089:Exocytosis; D053804:Granzymes; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D054353:Perforin; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; D002118:Calcium