title: Neuropathologic, phenotypic and functional analyses of Mucosal Associated Invariant T cells in Multiple Sclerosis.
abstract: The involvement of Mucosal Associated Invariant T (MAIT) cells, which are anti-microbial semi-invariant T cells, remains elusive in Multiple Sclerosis (MS).
  
  
  
  Deciphering the potential involvement of MAIT cells in the MS inflammatory process.
  
  
  
  By flow cytometry, blood MAIT cells from similar cohorts of MS patients and healthy volunteers (HV) were compared for frequency, phenotype, activation potential after in vitro TCR engagement by bacterial ligands and transmigration abilities through an in vitro model of blood-brain barrier. MS CNS samples were also studied by immunofluorescent staining and quantitative PCR.
  
  
  
  Blood MAIT cells from relapsing-remitting MS patients and HV presented similar frequency, ex vivo effector phenotype and activation abilities. MAIT cells represented 0.5% of the total infiltrating T cells on 39 MS CNS lesions. This is low as compared to blood frequency (p<0.001), but consistent with their low transmigration rate. Finally, transcriptional over-expression of MR1 - which presents cognate antigens to MAIT cells - and of the activating cytokines IL-18 and IL-23 was evidenced in MS lesions, suggesting that the CNS microenvironment is suited to activate the few infiltrating MAIT cells. Taken together, these data place MAIT cells from MS patients as minor components of the inflammatory pathological process.
authors.affiliation: INSERM, UMR 1064, Nantes F-44093, France; Nantes University, Medicine Department, Nantes F-44035, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Salou
authors.affiliation: INSERM, UMR 1064, Nantes F-44093, France; Nantes University, Medicine Department, Nantes F-44035, France.
authors.forename: Bryan
authors.initials: B
authors.lastname: Nicol
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; Nantes University, Medicine Department, Nantes F-44035, France; Nantes Hospital, ITUN, Nantes F-44093, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baron
authors.affiliation: INSERM, UMR 1064, Nantes F-44093, France; Nantes Hospital, Department of Neurology, Nantes, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Michel
authors.affiliation: INSERM, UMR 1064, Nantes F-44093, France; Nantes University, Medicine Department, Nantes F-44035, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Elong-Ngono
authors.affiliation: SFR François Bonamy, Cellular and Tissue Imaging Core Facility (MicroPICell), Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hulin
authors.affiliation: SFR François Bonamy, Cellular and Tissue Imaging Core Facility (MicroPICell), Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Nedellec
authors.affiliation: INSERM 015, Centre d'Investigation Clinique, Nantes, France.
authors.forename: Marylène
authors.initials: M
authors.lastname: Jacq-Foucher
authors.affiliation: INSERM 015, Centre d'Investigation Clinique, Nantes, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Le Frère
authors.affiliation: INSERM 015, Centre d'Investigation Clinique, Nantes, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Jousset
authors.affiliation: Nantes Hospital, Institut des Maladies de l'Appareil Digestif, CIC-04 Inserm, Nantes, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourreille
authors.affiliation: Nantes Hospital, Department of Neurology, Nantes, France; INSERM 015, Centre d'Investigation Clinique, Nantes, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Wiertlewski
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; Nantes University, Medicine Department, 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; Nantes Hospital, Department of Neurology, Nantes, France; INSERM 015, Centre d'Investigation Clinique, Nantes, France. Electronic address: David.laplaud@univ-nantes.fr.
authors.forename: David-Axel
authors.initials: DA
authors.lastname: Laplaud
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002465:Cell Movement; D005260:Female; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D008954:Models, Biological; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology* / Q000473:pathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; C000589760:IL18 protein, human; D020382:Interleukin-18; D053759:Interleukin-23; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell
keywords: Central Nervous System; Mucosal Associated T cells; Multiple Sclerosis; Neuroinflammation