Immunological studies on anca-associated vasculitis with special reference to T cell activation

Sammanfattning: This thesis focuses on the role of T cells in ANCA-associated vasculitis. We initially investigated activation markers on T cells in patients with Wegener s granulomatosis (WG), microscopic polyangiitis (MPA) and renal limited disease (RLD) and found increased expression indicating continuous activation despite clinical remission. As apoptosis maintains homeostatic control of lymphocyte populations we examined its role in WG, MPA and RLD in comparison with patients with rheumatoid arthritis, lupus erythematosus and Sjögren´s syndrome. We found that patients with ANCApositive vasculitis have high serum levels of soluble Fas (sFas) that remain elevated even in clinical remission. In our third paper we studied the influence of chemokines on the cell surface expression of thrombospondin-1 (TSP-1) in T cells. The results demonstrate a chemokine-dependent CD26-controlled regulation of T cell polarity and migration through endogenous TSP-1. Based on the results in the third paper we then studied patients with ANCA positive vasculitis with respect to serum levels of chemokines, T cell mRNA expression of chemokine receptors, and possible influence of CD26 on TSP-1 expression. We found altered chemokine levels and evidence for impaired CD26 suppression of chemokine- dependent TSP-1 expression in vasculitis patients in comparison with patients with asthma suggesting that a mechanism for negative regulation of T cell migration is suppressed in these patients. These findings suggest that T cells play an important role in ANCA associated vasculitis and may be useful targets in the development of therapeutic strategies.