Irregular cytokine pattern of CD4(+) T lymphocytes in response to Staphylococcus aureus in patients with Wegener's granulomatosis

The initial stage of Wegener's Granulomatosis (WG) is often marked by sympt oms of infection and it has been postulated that a bacterial infection coul d be the aetiologic factor of this disease. The objective of our work was t o investigate T-cell-mediated immunity in WG by testing proliferative respo nses on bacterial antigens and particularly Staphylococcus aureus. We inves tigated the bulk proliferative response of peripheral blood lymphocytes (PB L) from patients with clinically active WG to gram-positive bacteria and pu rified proteinase 3 (PR-3), the major target antigen of c-ANCA. We generate d S. aureus-specific PBL-derived T-cell lines and T-cell clones (TLC). In t wo WG patients 27 TLC were characterized in terms of reactivity to bacteria l antigens/PR-3, phenotype, HLA class II restriction and pattern of cytokin e secretion. Compared to coagulase-negative Staphylococci and beta-haemolyt ic Streptococci A, reactivity to S. aureus was significantly increased in a ll patients with WG. Using purified PR-3. we found a PBL proliferation in f ive out of 25 WG patients. The TLC were S. aureus-specific and did not cros s-recognize Streptococci or coagulase-negative Staphylococci. The S. aureus -specific TLC were of the alpha beta-TCR+ CD4(+) phenotype and HLA-DR-restr icted. These TLC predominantly showed a Th2-type of cytokine secretion. Int erestingly, seven of the S. aureus-reactive TLC also recognized the PR-3 an tigen. From these data we conclude that Staphylococci-specific HLA-DR-restr icted CD4(+) T cells may play a key role in the initial triggering of immun e responses in WG.