title: Differential outcome of tolerance induction in naive versus activated Theiler's virus epitope-specific CD8+ cytotoxic T cells.
abstract: Tolerance induced by the intravenous injection of peptide-pulsed, ethylene carbodiimide (ECDI)-fixed splenic antigen-presenting cells (Ag-SP) is a safe and effective method of inducing specific unresponsiveness in CD4+ T cells for the prevention and treatment of a variety of autoimmune diseases. We determined whether Ag-SP tolerance could also be used to tolerize CD8+ T cells. We show in the Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease model of multiple sclerosis that CD8+ T cells specific for both dominant and subdominant epitopes can be rendered tolerant. Interestingly, although virus clearance was delayed, lack of the virus-specific cytotoxic T-lymphocyte response did not result in the conversion of normally TMEV-resistant C57BL/6 mice to a susceptible phenotype. Importantly, we found that Ag-SP tolerance may not be a practical treatment for human diseases in which CD8+ T cells play a major role in pathogenesis, as tolerance induction in mice previously infected with TMEV led to a severe, often fatal reaction.
authors.affiliation: Department of Microbiology and Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Meghann Teague
authors.initials: MT
authors.lastname: Getts
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001327:Autoimmune Diseases / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002234:Carbodiimides / Q000737:chemistry; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000378:metabolism; D017945:Theilovirus / Q000235:genetics* / Q000276:immunology
chemical_list: D002234:Carbodiimides; D016207:Cytokines; D000939:Epitopes