title: Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis.
abstract: BACKGROUND
  Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. Perivascular cuffing and clusters of T cells in the affected cortical hemisphere are indicative of an active cellular immune response.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) and brain-infiltrating lymphocytes (BILs) were isolated from 20 RE surgery specimens by standard methods, and CD3(+) T cell populations were analyzed by flow cytometry. Gamma delta T cell receptor spectratyping was carried out by nested PCR of reversed transcribed RNA extracted from RE brain tissue, followed by high resolution capillary electrophoresis. A MiSeq DNA sequencing platform was used to sequence the third complementarity determining region (CDR3) of δ1 chains.
  
  
  RESULTS
  CD3(+) BILs from all of the RE brain specimens comprised both αβ and γδ T cells. The median αβ:γδ ratio was 1.9 (range 0.58-5.2) compared with a median ratio of 7.7 (range 2.7-40.8) in peripheral blood from the same patients. The αβ T cells isolated from brain tissue were predominantly CD8(+), and the majority of γδ T cells were CD4(-) CD8(-). Staining for the early activation marker CD69 showed that a fraction of the αβ and γδ T cells in the BILs were activated (median 42%; range 13-91%, and median 47%; range 14-99%, respectively). Spectratyping T cell receptor (TCR) Vδ1-3 chains from 14 of the RE brain tissue specimens indicated that the γδ T cell repertoire was relatively restricted. Sequencing δ1 chain PCR fragments revealed that the same prevalent CDR3 sequences were found in all of the brain specimens. These CDR3 sequences were also detected in brain tissue from 15 focal cortical dysplasia (FCD) cases.
  
  
  CONCLUSIONS
  Neuroinflammation in RE involves both activated αβ and γδ T cells. The presence of γδ T cells with identical TCR δ1 chain CDR3 sequences in all of the brain specimens examined suggests that a non-major histocompatibility complex (MHC)-restricted immune response to the same antigen(s) is involved in the etiology of RE. The presence of the same δ1 clones in CD brain implies the involvement of a common inflammatory pathway in both diseases.
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. geoffreyowens@mednet.ucla.edu.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Owens
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. kerickson@mednet.ucla.edu.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Erickson
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. ccmalone2014@gmail.com.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Malone
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, USA. calpan@gmail.com.
authors.forename: Calvin
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. mhuynh@mednet.ucla.edu.
authors.forename: My N
authors.initials: MN
authors.lastname: Huynh
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. jwchang@mednet.ucla.edu.|Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. jwchang@mednet.ucla.edu.
authors.forename: Julia W
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. tchirwa@mednet.ucla.edu.
authors.forename: Thabiso
authors.initials: T
authors.lastname: Chirwa
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. HVinters@mednet.ucla.edu.|Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. HVinters@mednet.ucla.edu.|Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. HVinters@mednet.ucla.edu.|Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. HVinters@mednet.ucla.edu.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA. gmathern@ucla.edu.|Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. gmathern@ucla.edu.|Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. gmathern@ucla.edu.|Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA. gmathern@ucla.edu.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mathern
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, 300 Stein Plaza, Ste. 562, Los Angeles, CA, 90095-6901, USA.|Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kruse
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D022801:Complementarity Determining Regions / Q000276:immunology / Q000502:physiology; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D004827:Epilepsy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology / Q000502:physiology*; D007223:Infant; D037181:Lectins, C-Type / Q000276:immunology / Q000502:physiology; D008297:Male; D065703:Malformations of Cortical Development, Group I / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D022801:Complementarity Determining Regions; D037181:Lectins, C-Type; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000099192:CD69 Antigens