Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen's encephalitis.
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.
Bien
Christian G
CG
Department of Epileptology, University of Bonn, Bonn, Germany. c.bien@uni-bonn.de
Bauer
Jan
J
Deckwerth
Thomas L
TL
Wiendl
Heinz
H
Deckert
Martina
M
Wiestler
Otmar D
OD
Schramm
Johannes
J
Elger
Christian E
CE
Lassmann
Hans
H
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
D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases