Characterization of the expanded T-cell populations in patients with Wegener's granulomatosis

Abstract

Objectives: Wegener's granulomatosis (WG) is a chronic inflammatory disease characterized by granulomatosis inflammation, systemic vasculitis and glomerulonephritis. In patients, the peripheral T cells are characterized by mono/oligoclonal CD4⁺/CD8⁺ T-cell AV/BV receptor expansions, with aberrant expression of activation markers. This study was designed to characterize the phenotypic differences between the expanded and nonexpanded T-cell populations. Expression of markers for activation, costimulation and adhesion molecules was examined. As earlier studies have shown aberrant expression of CD28/CD152, we also analysed the expression of another costimulatory system, the tumour necrotic factor receptor (TNFR) superfamily proteins. Design: Fluorocrome-conjugated monoclonal antibodies and flow cytometry was used to analyse the expression of the different markers on the surface of the expanded and nonexpanded subsets of T cells. Setting: The Karolinska Hospital and Karolinska Institutet in Stockholm, Sweden. Subjects: Nine patients with WG (six men and three women) had 16 TCRAV/BV CD4⁺/CD8⁺ expanded populations that were characterized. Results: The expanded TCRA/BV CD4⁺ and CD8⁺ cells had lower percentages of cells expressing CD28 and higher of those expressing CD152 (CTLA-4). The expanded CD4⁺ population had more cells expressing HLA-DR, CD57 and CCR5 (CD195), whilst the expression of CD25 was present on fewer of the expanded cells. The expanded CD8⁺ population contained more cells expressing CD137 (4-1BB), CD137 (4-1BBL), CD30 (Ki-1), CD40 and CD134 (OX40). Conclusions: There were marked differences in the phenotypes of expanded and nonexpanded T-cell populations.