Regulation of the proinflammatory effects of Fas ligand (CD95L).
Fas ligand (CD95L) inhibits T cell function in immune-privileged organs such as the eye and testis, yet in most tissues CD95L expression induces potent inflammatory responses. With a stably transfected colon carcinoma cell line, CT26-CD95L, the molecular basis for these divergent responses was defined. When injected subcutaneously, rejection of CT26-CD95L was caused by neutrophils activated by CD95L. CT26-CD95L survived in the intraocular space because of the presence of transforming growth factor-beta (TGF-beta), which inhibited neutrophil activation. Providing TGF-beta to subcutaneous sites protected against tumor rejection. Thus, these cytokines together generate a microenvironment that promotes immunologic tolerance, which may aid in the amelioration of allograft rejection.
Chen
J J
JJ
Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, 1150 West Medical Center Drive, 4520 Medical Science Research Building I, Ann Arbor, MI 48109-0650, USA.
Sun
Y
Y
Nabel
G J
GJ
D000818:Animals; D000867:Anterior Chamber; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology*; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases