Rheumatology Advance Access published online on March 17, 2008
Rheumatology, doi:10.1093/rheumatology/ken028
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T lymphocytes in patients with primary vasculitis: expansion of CD8 + T cells with the propensity to activate polymorphonuclear neutrophils
1Rheumatology, Department of Endocrinology, Diabetology and Rheumatology, Heinrich-Heine-University of Duesseldorf, 2Institute for Immunology, Ruprecht-Karls University of Heidelberg, 3Klinik für Unfallchirurgie und Orthopädie, Berufsgenossenschaftliche Unfallklinik Ludwigshafen and 4Medizinische Klinik, Ruprecht-Karls University of Heidelberg, Germany.
Correspondence to:
C. Iking-Konert, Rheumatology, Department of Endocrinology, Diabetology and Rheumatology, Heinrich-Heine-University of Duesseldorf, Moorenstr 5, 40225 Düsseldorf, Germany. E-mail: Iking-konert{at}med.uni-duesseldorf.de
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Abstract |
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Objectives. To gain insight into the immune pathogenesis of primary ANCA-associated vasculitides, the prevalence of circulating T lymphocytes expressing CD11b as a marker for activation was analysed in patients with WG or microscopic polyangiitis.
Methods. Receptor expression and IFN
synthesis were measured in T cells of patients with active disease by cytofluorometry and compared with expression in patients in remission and in healthy donors.
Results. During active disease, a small but conspicuous population of CD8+CD28+CD11b+ was found which produced IFN. In healthy donors and in patients in remission or undergoing immunosuppressive therapy, CD11b was exclusively associated with CD8+CD28– cells, the latter being more frequent in patients with long-lasting or severe disease. In vitro experiments confirmed that CD11b is up-regulated when T cells are activated. After multiple rounds of restimulation, the CD11b expression persists whereas CD28 expression is lost, compatible with the notion that CD8+CD28+CD11b+ represents a transient phenotype in the course of T-cell activation. The IFN-producing T cells activated polymorphonuclear neutrophils (PMN) to express MHC class II, thus generating the same PMN phenotype as in patients with active ANCA-associated vasculitis. A similar PMN phenotype could be generated by cultivation with supernatants of activated T cells or by IFN alone, but not by antibodies to proteinase 3.
Conclusions. In active primary vasculitis, a small population of CD8+ T cells, identified by the expression of CD11b, expands, producing IFN. These T cells could activate PMN, thus generating a long-living and potentially destructive PMN phenotype.
KEY WORDS: PMN, ANCA, Vasculitis, T cells, CD11b, CD28, CD8, WG, Microscopic polyangiitis
Submitted 5 September 2007;
revised version accepted 11 January 2008.
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