title: Target cell lysis by cytotoxic T lymphocytes that lack detectable hemolytic perforin activity.
abstract: When mouse target cells are subjected to cytolytic attack by mouse CTL cell lines that have been cultured for many months in high levels of IL-2, and have abundant perforin-rich secretory granules, they exhibit two prominent changes: 1) rapid and massive increase (greater than 10-fold) in intracellular Ca2+ concentration and 2) fragmentation of DNA into nucleosome-sized fragments. We show here that when the same target cells are subjected to cytolytic attack by perforin-deficient CTL, either human CTL or primary mouse CTL from peritoneal exudates, the same changes are observed, suggesting that perforin-rich and perforin-deficient CTL kill their target cells by similar (if not identical) mechanisms. It is possible that perforin-deficient CTL produce enough perforin to destroy target cells but not enough to be detected by currently available methods.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: N L
authors.initials: NL
authors.lastname: Allbritton
authors.forename: C
authors.initials: C
authors.lastname: Nagler-Anderson
authors.forename: T J
authors.initials: TJ
authors.lastname: Elliott
authors.forename: C R
authors.initials: CR
authors.lastname: Verret
authors.forename: H N
authors.initials: HN
authors.lastname: Eisen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D006461:Hemolysis; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D002118:Calcium