Regulatory T cell/Th17 balance in the pathogenesis of pediatric Behçet disease.

Abstract

OBJECTIVES\nBehçet disease (BD) is a chronic systemic inflammatory disorder of unknown aetiology. The aim of this study was to determine the orientation of T cell subpopulations in pediatric BD and more precisely to look for a regulatory T lymphocytes (Tregs)/Th17 imbalance.\n\n\nMETHODS\nT cell subpopulations were analyzed by flow cytometry in the peripheral blood of pediatric patients with acute (aBD, n\u2009=\u200924), remitting (rBD, n\u2009=\u200912) BD, and in healthy controls (HC, n\u2009=\u200924). Tregs (CD4+CD25hiCD127-/loFoxp3+), activated Tregs (GITR, LAP, CTLA-4, and HLA-DR expression), CD4+ and CD8+ T cells producing interferon-g (Th1 and Tc1) or interleukin (IL)-17 (Th17 and Tc17) under polyclonal (OKT3/IL-2) or antigenic (Streptococcus sanguis KTH-1 peptides and HSP-60) stimulation, were numerated.\n\n\nRESULTS\nTh17 (1.9 and 5.1 fold) and Tc17 (4.0 and 2.0 fold) frequency under mitogenic stimulation was significantly increased in aBD and rBD patients as compared with HC. Th17 frequency under antigenic stimulation was also higher in patients than in HC. The percentage and number of Tregs and activated Tregs in patients and in HC were similar. However, when Tregs were removed, antigen-driven differentiation into Th1 and Th17 was significantly boosted in BD but not in HC CD4+T cells.\n\n\nCONCLUSION\nThere is a bias toward a Th17 polarization in acute and remitting BD children. Although we did not observe an increase in the number of Tregs in these patients, their Tregs limit CD4+T cell differentiation into Th1 and Th17 cells. Thus, in pediatric BD, Tregs seem to incompletely counterbalance a Th17 orientation of the helper T cell response.