title: T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta.
abstract: OBJECTIVE
  T-helper 1 (Th1) and Th17 lymphocytes are involved in experimental autoimmune encephalomyelitis, the model of multiple sclerosis (MS). We characterized the Th1/Th17 cell populations in peripheral blood (PB), their interferon (IFN) receptor expression sensitivity to IFN-beta in MS patients.
  
  
  METHODS
  In 30 untreated patients with active MS (AMS) and 32 with inactive MS (IMS), and in 22 healthy subjects, we measured intracellular cytokine expression, interleukin-17-producing myelin basic protein-stimulated PB lymphocytes, surface IFN type I receptor chain1 (IFN-alphaR1) expression, IFN-beta-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation, and apoptosis of anti-CD3 monoclonal antibody-stimulated PB lymphocytes.
  
  
  RESULTS
  Th17 cell percentage increased around sevenfold in AMS compared with IMS or healthy subjects, but there was no change in Th1 cells. Th17 cells in AMS were myelin basic protein specific. The longitudinal follow-up of 18 MS patients shifting between AMS and IMS showed that the percentage of Th17 but not Th1 cells always increased in AMS. IFN-alphaR1 expression, IFN-beta-induced STAT1 activation, and apoptosis were significantly greater in Th17 than Th1 cells. IFN-alphaR1 expression and IFN-beta-dependent STAT1 activation progressively increased in vitro with a highly significant positive correlation only in developing Th17 but not in Th0 or Th1 cells.
  
  
  CONCLUSIONS
  Evidence that an expansion of peripheral Th17 cells, a Th subset that can infiltrate brain parenchyma and damage cells, is associated with disease activity in MS. The greater IFN-alphaR1 level expressed by Th17 compared with Th1 cells might make them a selective target for IFN-beta therapy.
authors.affiliation: Department of Clinical and Biological Sciences, Division of Neurology, San Luigi Gonzaga School of Medicine, Orbassano (Torino), Turin, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Durelli
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.forename: Marinella
authors.initials: M
authors.lastname: Clerico
authors.forename: Daniela
authors.initials: D
authors.lastname: Boselli
authors.forename: Giulia
authors.initials: G
authors.lastname: Contessa
authors.forename: Paolo
authors.initials: P
authors.lastname: Ripellino
authors.forename: Bruno
authors.initials: B
authors.lastname: Ferrero
authors.forename: Pierre
authors.initials: P
authors.lastname: Eid
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology; D016009:Chi-Square Distribution; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000378:metabolism / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000473:pathology*; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D017304:Annexin A5; D015703:Antigens, CD; D007155:Immunologic Factors; D020381:Interleukin-17; D053633:Receptor, Interferon alpha-beta; D003609:Dactinomycin; C025942:7-aminoactinomycin D; D016899:Interferon-beta