T lymphocytes in patients with primary vasculitis: expansion of CD8+ T cells with the propensity to activate polymorphonuclear neutrophils

Autor: Ellen Bleck, Matthias Schneider, C Iking-Konert, Benedikt Ostendorf, T. Vogl, K. Andrassy, Oliver Sander, C. Wagner, G. M. Hänsch, B. Prior
Rok vydání: 2008
Předmět:
Zdroj: Rheumatology. 47:609-616
ISSN: 1462-0332
1462-0324
DOI: 10.1093/rheumatology/ken028
Popis: 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 IFNsynthesis 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 CD8þCD28þCD11bþ was found which produced IFN� . In healthy donors and in patients in remission or undergoing immunosuppressive therapy, CD11b was exclusively associated with CD8þCD28� 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 CD8þCD28þCD11bþ 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 CD8þ 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.
Databáze: OpenAIRE