title: Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen's encephalitis.
abstract: Rasmussen's encephalitis is a progressive epileptic disorder characterized by unihemispheric lymphocytic infiltrates, microglial nodules, and neuronal loss leading to the destruction of the affected hemisphere. In this study, immunohistochemical evaluation of specimens from 11 patients revealed lymphocytic infiltrates that consisted mainly of CD3(+)CD8(+) T cells. Of these cells, 7.0% lay in direct apposition to MHC class I(+) neurons. Confocal laser microscopy revealed that these lymphocytes contained granzyme B in a polar orientation toward these perikarya. Single neurons underwent apoptosis. These findings indicate that a T-cell-mediated cytotoxic reaction induces neuronal death in Rasmussen's encephalitis. This study directly shows, for what we believe is the first time, that a cytotoxic T-cell mechanism contributes to loss of neurons in human brain disease.
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany. c.bien@uni-bonn.de
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Deckwerth
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D053804:Granzymes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases