The fungal metabolite gliotoxin: immunosuppressive activity on CTL-mediated cytotoxicity.
Gliotoxin, a potential etiologic agent which is synthesized by Aspergillus fumigatus and other pathogenic fungi, exhibits a variety of immunosuppressive activities. We have found that gliotoxin markedly inhibits both perforin-dependent and Fas ligand-dependent cytotoxic T-lymphocyte (CTL)-mediated cytotoxicity. Gliotoxin blocked granule exocytosis and the production of inositol phosphates in response to anti-CD3 stimulation. Apparently, activation signals were not efficiently received by the gliotoxin-treated CTL clone, perhaps because gliotoxin profoundly disturbed CTL cell attachment to immobilized anti-CD3. Although the expression of surface molecules of the CTL clone such as CD3 was unaffected by gliotoxin, the effector/target conjugate formation was inhibited dose-dependently by gliotoxin treatment of the effector CTL clone. These results suggest that gliotoxin prevents CTL from interacting with target cells.
Yamada
A
A
Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
Kataoka
T
T
Nagai
K
K
D000818:Animals; D001232:Aspergillus fumigatus / Q000378:metabolism; D004220:Disulfides; D053222:Fas Ligand Protein; D005912:Gliotoxin / Q000737:chemistry / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004220:Disulfides; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D005912:Gliotoxin