Differential outcome of tolerance induction in naive versus activated Theiler's virus epitope-specific CD8+ cytotoxic T cells.
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.
Getts
Meghann Teague
MT
Department of Microbiology and Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Kim
Byung S
BS
Miller
Stephen D
SD
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
D002234:Carbodiimides; D016207:Cytokines; D000939:Epitopes