CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing

Schneider-Hohendorf, Tilman; Mohan, Hema; Bien, Christian G.; Breuer, Johanna; Becker, Albert; Görlich, Dennis; Kuhlmann, Tanja; Widman, Guido; Herich, Sebastian; Elpers, Christiane; Melzer, Nico; Dornmair, Klaus; Kurlemann, Gerhard; Wiendl, Heinz; Schwab, Nicholas (2016): CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing. In: Nature Communications, Vol. 7, 11153

Abstract

Rasmussen encephalitis (RE) is a rare paediatric epilepsy with uni-hemispheric inflammation and progressive neurological deficits. To elucidate RE immunopathology, we applied T-cell receptor (TCR) sequencing to blood (n = 23), cerebrospinal fluid (n = 2) and brain biopsies (n = 5) of RE patients, and paediatric controls. RE patients present with peripheral CD8(+) T-cell expansion and its strength correlates with disease severity. In addition, RE is the only paediatric epilepsy with prominent T-cell expansions in the CNS. Consistently, common clones are shared between RE patients, who also share MHC-I alleles. Public RE clones share V beta genes and length of the CDR3. Rituximab/natalizumab/basiliximab treatment does not change TCR diversity, stem cell transplantation replaces the TCR repertoire with minimal overlap between donor and recipient, as observed in individual cases. Our study supports the hypothesis of an antigen-specific attack of peripherally expanded CD8(+) lymphocytes against CNS structures in RE, which might be ameliorated by restricting access to the CNS.

• Item Type: Journal article
• Faculties: Medicine > Institute for Immunology
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2041-1723
• Language: English