title: Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis.
abstract: OBJECTIVE
  In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8(+) T cells. These clones have been assumed - but never demonstrated - to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8(+) T cells in the disease.
  
  
  METHODS
  For the first time, TCR Vβ repertoire from paired blood (purified CD8(+) and CD4(+) T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8(+) T cells were characterized by fluorescent staining.
  
  
  RESULTS
  TCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8(+) T cells. In parallel, we showed that blood oligoclonal CD8(+) T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B.
  
  
  CONCLUSIONS
  This study highlights the predominant implication of CD8(+) T cells in MS pathophysiology and demonstrates that potentially aggressive CD8(+) T cells can be easily identified and characterized from blood and CSF samples.
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Salou
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Garcia
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Neurology Department, Nantes Hospital Nantes, F-44093, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Michel
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gainche-Salmon
authors.affiliation: Pathology Department, Nantes Hospital Nantes, F-44093, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Loussouarn
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France.
authors.forename: Bryan
authors.initials: B
authors.lastname: Nicol
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Guillot
authors.affiliation: SFR François Bonamy, Cellular and Tissue Imaging Core Facility (MicroPICell) Nantes, F-44093, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hulin
authors.affiliation: SFR François Bonamy, Cellular and Tissue Imaging Core Facility (MicroPICell) Nantes, F-44093, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Nedellec
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baron
authors.affiliation: LINA UMR6241, Nantes University Nantes, F-44093, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Ramstein
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
authors.forename: Arnaud B
authors.initials: AB
authors.lastname: Nicot
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Degauque
authors.affiliation: INSERM, UMR 1064 Nantes, F-44093, France ; Neurology Department, Nantes Hospital Nantes, F-44093, France ; INSERM 004, Centre d'Investigation Clinique Nantes, F-44093, France.
authors.forename: David A
authors.initials: DA
authors.lastname: Laplaud