title: Clonal expansions of pathogenic CD8+ effector cells in the CNS of myelin mutant mice.
abstract: Tissue damage in the CNS is critically influenced by the adaptive immune system. Primary oligodendrocyte damage (by overexpression of PLP) leads to low-grade inflammation of high pathological impact, which is mediated by CD8+ T cells. To yield further insight into pathogenesis and nature of immune responses in myelin mutated mice, we here apply a detailed immunological characterization of CD8+ T cells in PLP-transgenic and aged wild type mice. We provide evidence that T effector cells accumulate in the CNS of PLP-transgenic and wild-type mice and show a higher level of activation in mutant mice, indicated by surface markers and clonal expansions, as demonstrated by T cell receptor CDR3-spectratype analysis. Vbeta-Jbeta similarities suggest specificity against a common antigen, albeit we could not find specific responses against myelin-antigen-derived peptides. The association of primary oligodendrocyte damage with secondary expansions of pathogenic cells underlines the role of adaptive immune reactions in neurodegenerative and neuroinflammatory diseases.
authors: Department of Neurology, University of Wuerzburg, D-97080 Wuerzburg, Germany.
authors: C
authors: C
authors: Leder
authors: N
authors: N
authors: Schwab
authors: C W
authors: CW
authors: Ip
authors: A
authors: A
authors: Kroner
authors: K-A
authors: KA
authors: Nave
authors: K
authors: K
authors: Dornmair
authors: R
authors: R
authors: Martini
authors: H
authors: H
authors: Wiendl
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002999:Clone Cells / Q000276:immunology; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D007107:Immune System / Q000276:immunology* / Q000503:physiopathology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D016827:CD8 Antigens