title: Vaccination leads to an aberrant FOXP3 T-cell response in non-remitting juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To investigate how meningococcal C vaccination in patients with remitting (oligoarticular) or progressive (polyarticular) juvenile idiopathic arthritis (JIA) influences the specific T-cell response to both the vaccine and heat shock protein 60, a regulatory auto-antigen in JIA.
  
  
  METHODS
  Twenty six oligoarticular, 28 polyarticular JIA patients and 20 healthy adults were studied before and after MenC vaccination in a prospective follow-up study. T-cell proliferation assay, flow cytometry, carboxyfluorescein diacetate succinimidyl ester staining and multiplex immunoassay were performed to quantify and qualify the antigen-specific immune responses.
  
  
  RESULTS
  Peripheral blood mononuclear cells (PBMC) from polyarticular JIA exemplified higher antigen-specific CD4 T-cell proliferation, interleukin 2 (IL-2) and tumour necrosis factor alpha (TNFα) production when compared with oligoarticular JIA or healthy individuals after vaccination. Furthermore, in polyarticular JIA antigen-induced CD4+CD25(bright) or CD4+FOXP3+ T cells did not increase upon vaccination.
  
  
  CONCLUSIONS
  Polyarticular JIA CD4+FOXP3+ T cells did not respond to vaccination and demonstrated a higher percentage of cells irrespective of vaccination when compared with oligoarticular JIA. These cells are either activated T cells and/or regulatory cells unable to regulate the antigen-specific immune response after vaccination. When compared with oligoarticular JIA, the increased IL-2 and TNFα production underline the immune hyperresponsiveness of polyarticular JIA PBMC to an antigenic trigger. As this may hold a risk for derailment, these findings could provide a cellular basis for the presumed relationship between environmental triggers and disease in human autoimmune diseases.
authors.affiliation: Department of Pediatrics, Center for Cellular and Molecular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Arash
authors.initials: A
authors.lastname: Ronaghy
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Evelien
authors.initials: E
authors.lastname: Zonneveld-Huijssoon
authors.forename: Mark R
authors.initials: MR
authors.lastname: Klein
authors.forename: Femke
authors.initials: F
authors.lastname: van Wijk
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Wietse
authors.initials: W
authors.lastname: Kuis
authors.forename: Nico M
authors.initials: NM
authors.lastname: Wulffraat
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000097:blood*; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D022401:Meningococcal Vaccines / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D018834:Chaperonin 60; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D022401:Meningococcal Vaccines; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D018074:Vaccines, Conjugate