Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides.
There is substantial evidence that T-cells are off balance in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Genetic risk factors may influence shaping of the TCR repertoire and regulatory control of T-cells in predisposed individuals. T-cells are found in inflammatory lesions. Vigorous Th1-type responses are seen in Wegener's granulomatosis and microscopic angiitis, whereas a Th2-type response predominates in Churg-Strauss syndrome. Oligoclonality and shortened telomers indicate antigen-driven clonal expansion and replicative senescence of T-cells in ANCA-associated vasculitides. Potent CD28(-) Th1-type cells displaying an effector-memory/late differentiated, senescent phenotype are expanded in peripheral blood and are found in granulomatous lesions in Wegener's granulomatosis. Differences in proliferative peripheral blood T-cell responses to the autoantigens proteinase 3 (PR3)- and myeloperoxidase (MPO) have not consistently been detected between patients with ANCA-associated vasculitides and healthy controls in vitro. To recognize an autoantigen, break tolerance, and maintain autoimmune disease T- and B-cells require particular triggers and lymphoid structures. There is preliminary evidence of lymphoid-like structures and possible maturation of autoreactive PR3-ANCA-specific B-cells in granulomatous lesions in Wegener's granulomatosis. Alteration of the T-cell response and anomalous autoantigen-presentation in lymphoid-structures could facilitate development of autoimmune disease in ANCA-associated vasculitides.
Lamprecht
P
P
Department of Rheumatology, University Hospital of Schleswig-Holstein, 23538 Luebeck, Germany. lamprecht@rheuma-zentrum.de
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D001327:Autoimmune Diseases / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D020022:Genetic Predisposition to Disease; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D016207:Cytokines