title: Cutting edge: neuronal recognition by CD8 T cells elicits central diabetes insipidus.
abstract: An increasing number of neurologic diseases is associated with autoimmunity. The immune effectors contributing to the pathogenesis of such diseases are often unclear. To explore whether self-reactive CD8 T cells could attack CNS neurons in vivo, we generated a mouse model in which the influenza virus hemagglutinin (HA) is expressed specifically in CNS neurons. Transfer of cytotoxic anti-HA CD8 T cells induced an acute but reversible encephalomyelitis in HA-expressing recipient mice. Unexpectedly, diabetes insipidus developed in surviving animals. This robust phenotype was associated with preferential accumulation of cytotoxic CD8 T cells in the hypothalamus, upregulation of MHC class I molecules, and destruction of vasopressin-expressing neurons. IFN-γ production by the pathogenic CD8 T cells was necessary for MHC class I upregulation by hypothalamic neurons and their destruction. This novel mouse model, in combination with related human data, supports the concept that autoreactive CD8 T cells can trigger central diabetes insipidus.
authors.affiliation: INSERM, U1043, Toulouse F-31300, France.
authors.forename: Tanja
authors.initials: T
authors.lastname: Scheikl
authors.forename: Béatrice
authors.initials: B
authors.lastname: Pignolet
authors.forename: Cécile
authors.initials: C
authors.lastname: Dalard
authors.forename: Sabine
authors.initials: S
authors.lastname: Desbois
authors.forename: Danièle
authors.initials: D
authors.lastname: Raison
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Abdelhadi
authors.initials: A
authors.lastname: Saoudi
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Hélène
authors.initials: H
authors.lastname: Hardin-Pouzet
authors.forename: Roland S
authors.initials: RS
authors.lastname: Liblau
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003919:Diabetes Insipidus / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000235:genetics / Q000276:immunology; D005805:Genes, MHC Class I; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009474:Neurons / Q000276:immunology* / Q000378:metabolism*; D014667:Vasopressins / Q000096:biosynthesis
chemical_list: D014667:Vasopressins; D007371:Interferon-gamma