Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides

Clin Exp Immunol. 2005 Aug;141(2):201-10. doi: 10.1111/j.1365-2249.2005.02808.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / analysis*
  • Autoimmune Diseases / immunology*
  • Cytokines / biosynthesis
  • Genetic Predisposition to Disease
  • Humans
  • T-Lymphocyte Subsets / immunology*
  • Vasculitis / immunology*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Cytokines