NDT Advance Access published online on August 22, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn461
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CD4+CD25+ T-cell populations expressing CD134 and GITR are associated with disease activity in patients with Wegener's granulomatosis
1 Department of Nephrology, University Duisburg-Essen 2 Department of Rheumatology and Clinical Immunology, Kliniken Essen Süd 3 Institute of Pathology and Neuropathology, University Duisburg-Essen 4 Department of Pneumology/Allergy, Ruhrlandklinik Essen 5 Department of Hematology, University Duisburg-Essen, Germany 6 Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, The Netherlands
Correspondence and offprint requests to: Oliver Witzke, Department of Nephrology, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany. Tel: +49-201-723-3955; Fax: +49-201-723-3393; E-mail: oliver.witzke{at}uk-essen.de
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Abstract |
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Background. An increased CD4+ CD25+ T-cell population is observed in Wegener's granulomatosis (WG). This T-cell population is not well characterized yet and their contribution to the disease pathogenesis remains obscure.
Methods. Thirty patients with WG and 18 healthy controls (HC) were included in this study. The disease activity and extension were measured by the Birmingham Vasculitis Activity Score (BVAS) and the Disease Extent Index (DEI). Lymphocytes from peripheral blood were analysed by FACS for the expression of CD4, CD25, CD134 and GITR. Cytokine expression in these subsets was assessed too. Nasal, lung and renal tissues from WG patients were immunohistochemically stained for CD3 and CD134.
Results. The percentage of CD134+ as well as GITR+ expressing CD4+CD25+ lymphocytes was increased in patients as compared to HC (37 ± 12% versus 27 ± 8%, P = 0.005; 18 ± 9% versus 11 ± 6%, P = 0.003). The expression of CD134 and GITR showed a significant correlation with disease activity (r = 0.5, P = 0.009; r = 0.55, P = 0.001). Most of these displayed the phenotype of effector memory T-cells (94 ± 4% and 91 ± 6%). CD134 T-cells were found in tissues affected by WG.
Conclusions. CD4+CD25+ effector memory T-cells expressing CD134 and GITR seem to play a role in disease mechanisms, as suggested by their close association with disease activity and their participation in inflammatory process.
Keywords: ANCA; CD134; GITR; Treg; Wegener's granulomatosis
Received for publication: 3. 3.08
Accepted in revised form: 22. 7.08