Enhancement of redirected target cell lysis by cytotoxic T lymphocytes in the presence of cytochalasin B.
The cytochalasins are known secretogogues. Their function as such is examined in light of the granule exocytosis model for lymphocyte-mediated cytotoxicity. Cytochalasin B is found to enhance target cell lysis by cytotoxic T lymphocytes when antibody-coated polystyrene beads are used to bridge the cells. The pattern of lysis is found to be biphasic in its dependence on cytochalasin B. Secretion of the enzyme BLT-esterase from the effector cells parallels the cytochalasin concentration-dependent pattern of lysis. Cytochalasin D is also able to enhance lysis but at concentrations less than cytochalasin B. Cytochalasin B does not inhibit binding of breads to the effector cell. This is shown by the ability of fluorescent beads coated with antibody to bind with an appropriate specificity to cells. These studies indicate that cytochalasin B is not strictly inhibitory for the induction of target cell lysis but can enhance lymphocyte-mediated lysis at low drug concentrations. These results are compatible with the interpretation that target cell lysis is mediated through a secretion process from cytotoxic T lymphocytes.
Kolber
M A
MA
Department of Medicine, University of Miami School of Medicine, Florida 33101.
D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology*; D015638:Cytochalasin D / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects; D053804:Granzymes; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D011137:Polystyrenes; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D011137:Polystyrenes; D011948:Receptors, Antigen, T-Cell; D015638:Cytochalasin D; D003571:Cytochalasin B; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human