Bystander CD8 T cell-mediated demyelination after viral infection of the central nervous system.
Multiple sclerosis, a chronic inflammatory disease of the CNS, is characterized by immune-mediated demyelination. Many patients have a remitting-relapsing course of disease with exacerbations often following unrelated microbial illnesses. The relationship between the two events remains obscure. One possibility is that T cells specific for the inciting microbial pathogen are able to effect demyelination at a site of ongoing inflammation within the CNS. This possibility was examined in mice infected with mouse hepatitis virus, a well-described model of virus-induced demyelination. Using transgenic TCR/recombination activation gene 2(-/-) mice with only non-mouse hepatitis virus-specific T cells, we show that CD8 T cells are able to cause demyelination in the absence of cognate Ag in the CNS, but only if specifically activated. These findings demonstrate a novel mechanism for immune-mediated neuropathology and show that activated CD8 T cells may serve as important mediators of bystander demyelination during times of infection, including in patients with multiple sclerosis.
Haring
Jodie S
JS
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Pewe
Lecia L
LL
Perlman
Stanley
S
D000818:Animals; D024201:Bystander Effect; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020805:Central Nervous System Viral Diseases / Q000150:complications*; D018925:Chemokines / Q000096:biosynthesis; D018352:Coronavirus Infections / Q000150:complications; D016207:Cytokines / Q000096:biosynthesis; D020278:Demyelinating Autoimmune Diseases, CNS / Q000209:etiology* / Q000276:immunology; D018398:Homeodomain Proteins / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000209:etiology; D006517:Murine hepatitis virus
D018925:Chemokines; D016207:Cytokines; D018398:Homeodomain Proteins; C064658:RAG-1 protein