Regulation of the Fas lytic pathway in cloned CTL.
Cloned murine CTL activated via the TCR or by PMA and ionomycin up-regulate surface Fas ligand and show an increased ability to kill non-Ag-specific Fas+ target cells. This up-regulation starts after 45 to 60 min and has a t1/2 for reversal of about 90 min. Up-regulation of lytic function is accompanied by up-regulation of Fas ligand on the CTL surface, which can be blocked by protein synthesis inhibitors. When up-regulation of Fas lytic function was induced by PMA and ionomycin, EGTA blocked both activation of lytic function and expression of Fas ligand detected by FACS analysis. However, when up-regulation was induced by specific Ag, EGTA blocked activation of lytic function, but not up-regulation of Fas ligand. Moreover, EL-4 cells have very high levels of surface Fas ligand, although they are not cytotoxic. Thus, expression of surface Fas ligand may be required, but not sufficient, for Fas-mediated lysis.
Glass
A
A
Department of Biology, University of California, Los Angeles 90095, USA.
Walsh
C M
CM
Lynch
D H
DH
Clark
W R
WR
D000818:Animals; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D053222:Fas Ligand Protein; D015759:Ionomycin / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology*; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate