Vaccination leads to an aberrant FOXP3 T-cell response in non-remitting juvenile idiopathic arthritis

Ann Rheum Dis. 2011 Nov;70(11):2037-43. doi: 10.1136/ard.2010.145151. Epub 2011 Aug 22.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arthritis, Juvenile / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Chaperonin 60 / immunology
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / blood*
  • Humans
  • Infant
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Meningococcal Vaccines / immunology*
  • T-Lymphocyte Subsets / immunology
  • Tetanus Toxoid / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vaccination
  • Vaccines, Conjugate / immunology

Substances

  • Chaperonin 60
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2
  • Meningococcal Vaccines
  • Tetanus Toxoid
  • Tumor Necrosis Factor-alpha
  • Vaccines, Conjugate