Destruction of Neurons by Cytotoxic T Cells: A New Pathogenic Mechanism in Rasmussen[ssquote]s Encephalitis.
Abstract number :
2.038
Submission category :
Year :
2001
Submission ID :
2322
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
C.G. Bien, MD, Epileptology, University of Bonn, Bonn, Germany; J. Bauer, PhD, Neuroimmunology, Institute of Brain Research, Vienna, Austria; T.L. Deckwerth, PhD, Idun Pharmaceuticals, San Diego, CA; M. Deckert, MD, Neuropathology, University of Bonn, Bon
RATIONALE: Rasmussen[ssquote]s encephalitis (RE) is a progressive epileptic disorder characterized by unihemispheric lymphocytic infiltrates, microglial nodules and neuronal loss leading to the destruction of the affected hemisphere. This study was performed to evaluate the pathogenic role of the cellular immune components, namely lymphocytes, in RE.
METHODS: We performed an immunohistochemical study of brain specimens of eleven patients with RE.
RESULTS: The lymphocytic infiltrates consisted mainly of CD3+CD8+ T cells. 7.0% of these cells laid in direct apposition to MHC class I+ neurons. Confocal laser microscopy revealed that these lymphocytes contained Granzyme B in a polar orientation towards these perikarya. Single neurons underwent apoptosis.
CONCLUSIONS: These findings indicate that a T cell-mediated cytotoxic reaction induces neuronal death in RE. This study for the first time directly shows that a cytotoxic T cell mechanism contributes to loss of neurons in human brain disease. It may provide a basis for the introduction of more specific immunosuppressive therapeutic strategies in RE.