title: Cutting edge: Multiple sclerosis-like lesions induced by effector CD8 T cells recognizing a sequestered antigen on oligodendrocytes.
abstract: CD8 T cells are emerging as important players in multiple sclerosis (MS) pathogenesis, although their direct contribution to tissue damage is still debated. To assess whether autoreactive CD8 T cells can contribute to the pronounced loss of oligodendrocytes observed in MS plaques, we generated mice in which the model Ag influenza hemagglutinin is selectively expressed in oligodendrocytes. Transfer of preactivated hemagglutinin-specific CD8 T cells led to inflammatory lesions in the optic nerve, spinal cord, and brain. These lesions, associating CD8 T cell infiltration with focal loss of oligodendrocytes, demyelination, and microglia activation, were very reminiscent of active MS lesions. Thus, our study demonstrates the potential of CD8 T cells to induce oligodendrocyte lysis in vivo as a likely consequence of direct Ag-recognition. These results provide new insights with regard to CNS tissue damage mediated by CD8 T cells and for understanding the role of CD8 T cells in MS.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 563, Toulouse, France.
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Tanja
authors.initials: T
authors.lastname: Scheikl
authors.forename: Jacques
authors.initials: J
authors.lastname: Zappulla
authors.forename: Marc
authors.initials: M
authors.lastname: Audebert
authors.forename: Sabine
authors.initials: S
authors.lastname: Desbois
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Roland S
authors.initials: RS
authors.lastname: Liblau
authors.forename: Lennart T
authors.initials: LT
authors.lastname: Mars
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D009186:Myelin Sheath / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology*
chemical_list: D000941:Antigens; D006388:Hemagglutinins