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

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 (TNF alpha) 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 TNF alpha 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.