Fas and Fas ligand enhance the pathogenesis of experimental allergic encephalomyelitis, but are not essential for immune privilege in the central nervous system.
Mutations of CD95 and CD95L, lpr and gld, respectively, are associated with spontaneous autoimmune disease and alteration of immune privilege. In lpr or gld animals these processes would be expected to exacerbate experimental allergic encephalomyelitis (EAE), an animal model of the autoimmune demyelinating disease multiple sclerosis. However, here we show that the lpr and gld mutations did not overcome the MHC-defined limits of disease and, surprisingly, did not exacerbate the pathology of EAE on a sensitive haplotype. In fact, the mutations dramatically ameliorated clinical signs of EAE without affecting the development of a Th1 response or inflammatory cell infiltration into the central nervous system. Fewer apoptotic cells were detected in inflammatory lesions of lpr mice than in wild-type lesions of similar severity. Our results indicate that CD95L is not an instrumental component of immune privilege in the central nervous system, and that functional CD95 and CD95L are important for the progression of clinical disease.
Sabelko
K A
KA
Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110, USA.
Kelly
K A
KA
Nahm
M H
MH
Cross
A H
AH
Russell
J H
JH
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D053222:Fas Ligand Protein; D006168:Guinea Pigs; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D004676:Myelin Basic Protein / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D019014:fas Receptor