T and B cell responses to neutrophil cytoplasmic antigens in systemic vasculitis.
The systemic vasculitides (SV) are characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens (ANCA). The role of T cells in SV is uncertain. We studied human and murine T cell responses to human neutrophil cytoplasmic antigens in vitro. T cells from mice immunized with the neutrophil extract showed dose-dependent antigen-specific proliferation, restricted by the MHC class II E molecule. Myeloperoxidase (MPO) was not an important target antigen for murine T cells. Peripheral blood lymphocytes (PBLs) were obtained from 36 patients with SV, 31 before the start of immunosuppressive therapy, and from 11 healthy controls. T cell responses to the neutrophil extract in vitro did not differ between patients and controls: there were only low levels of antigen-specific proliferation, and this could not be amplified by in vitro selection. In 3 patients and 2 normals, PBLs were also tested after the depletion of CD8+ cells; this did not unmask T cell reactivity to neutrophil extract. The lack of demonstrable T cell reactivity to this antigen preparation may indicate that T cells do not play an important effector role in these diseases. A solid-phase spot ELISA was adapted to demonstrate autoantibody-producing B cells in vitro. Low numbers of ANCA-producing B cells could be demonstrated in the majority of patients. B cells producing antibody to MPO could be demonstrated in most patients and in three laboratory staff, but not in normals from outside the laboratory. In 2 patients, sequential B cell spot ELISAs were performed during the introduction of therapy, and autoantibody-producing B cells rapidly decreased in number. This assay may therefore be useful in monitoring the effects of treatment at the cellular level.
Mathieson
P W
PW
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, United Kingdom.
Lockwood
C M
CM
Oliveira
D B
DB
D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000648:ultrastructure*; D013601:T-Lymphocytes / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
D000941:Antigens; D001323:Autoantibodies