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Activated CD4+ and CD8+ T-cell subsets in Wegener's granulomatosis

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Abstract

Several lines of evidence argue in favour of an involvement of T cells in the pathogenesis of Wegener's granulomatosis (WG). These include the presence of highly specific IgG autoantibodies to proteinase 3, perivascular T-cell infiltrates and elevated amounts of soluble interleukin-2 (IL-2) receptors in patient's serum. In order to further address this question we evaluated by double immunoflourescence and flow cytometry the expression of several cell surface molecules associated with T-cell activation. As compared to healthy controls (n=15), the CD4+ subset was significantly diminished, while the percentage of CD8+ T cells was elevated in WG patients (n=24). Within the CD4+ T-cell subset we found a highly significant increase in activation/memory markers (CD25, CD29, HLA-DR). Within the CD8+ T-cell subset the expression of CD11b, CD29 and CD57 was significantly elevated, while the expression of VD28 was reduced. The use of 10 Vβ-, 1 Vα-and 1 Vγ-specific monoclonal reagents failed to reveal any significant bias in the peripheral T-cell receptor V-gene repertoire of WG patients. There was also no correlation between T-cell activation markers and laboratory parameters [C-reactive protein (CRP), ESR], disease duration or therapy. A significant correlation was found only for the degree of organ involvement and the increase in CD4+ T cells coexpressing HLA-DR, as well as the increase in CD57 expression on CD8+ T cells. In conclusion, both CD4+ and CD8+ T-cell subsets were activated in WG. Cytotoxic CD8+ CD57+ CD11b+ CD28 T cells may directly contribute to damage of vascular endothelium.

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Schlesier, M., Kaspar, T., Gutfleisch, J. et al. Activated CD4+ and CD8+ T-cell subsets in Wegener's granulomatosis. Rheumatol Int 14, 213–219 (1995). https://doi.org/10.1007/BF00262300

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