CTX-B inhibits CTL cytotoxicity and cytoskeletal movements.
Binding of cytotoxic T lymphocytes (CTL) to specific targets induces cytoskeletal movements in the effector cell followed by delivery of the lethal hit which ultimately results in target cell lysis. The question whether movement of the cytoskeleton in CTL are obligatory for delivery of the lethal hit is not resolved. Here we report that the CTX-B subunit of cholera toxin which is devoid of the catalytic CTX-A subunit inhibits CTL function. Inhibition was found not to be due to interference with TCR expression, CTL-target conjugate formation, target induced transmembrane signalling or secretion of BLT-esterase. CTX-B however does interfere with F-actin patch formation at the effector target binding site and inhibits reorientation of the microtubule organizing center and Golgi apparatus towards the target binding site. It is concluded that interference with cytoskeletal movements is responsible for inhibition of cytolysis pointing to an important role of the cytoskeleton in the lytic reaction.
Sugawara
S
S
Department of Microbiology, University of Southern California School of Medicine, Los Angeles 90033.
Kaslow
H R
HR
Dennert
G
G
D000199:Actins / Q000032:analysis; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D003599:Cytoskeleton / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects; D053804:Granzymes; D007295:Inositol Phosphates / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012697:Serine Endopeptidases / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; D007295:Inositol Phosphates; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D000242:Cyclic AMP; D053804:Granzymes; D012697:Serine Endopeptidases