ACTIVATED CD4(+) AND CD8(+) T-CELL SUBSETS IN WEGENERS GRANULOMATOSIS

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 V beta-, 1 V alpha- and 1 V gamma-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.