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

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 gamma 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 gamma. 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 gamma-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 gamma. These T cells could activate PMN, thus generating a long-living and potentially destructive PMN phenotype.