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.
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Jodie S
JS
Haring
Lecia L
LL
Pewe
Stanley
S
Perlman
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