T cell receptor (TCR) V gene usage in patients with systemic necrotizing vasculitis

Clin Exp Immunol. 1995 Aug;101(2):213-9. doi: 10.1111/j.1365-2249.1995.tb08341.x.

Abstract

Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN) are systemic necrotizing vasculitides of unknown etiology. These disorders run a fatal course if untreated. T lymphocytes are implicated in the pathogenesis of WG, since they have been found to infiltrate affected organs, and sIL-2R correlates with disease activity. To elucidate further the role of T cells in necrotizing vasculitis, we have used a panel of 12 TCR V-specific MoAbs to investigate the number of cells expressing certain V alpha and V beta gene segments in the CD4+ and CD8+ subsets of altogether 11 patients with WG or PAN. In the group of patients, we found abnormal expansions of T cells using particular TCR V alpha or V beta gene products. These T cell expansions were more numerous, of a dramatically higher magnitude, and frequently more often found in the CD4 subset, compared with T cell expansions identified in healthy individuals. In long-term studies of the T cell expansions for up to 18 months, a heterogeneous pattern was revealed, with no obvious correlation to clinical features such as disease activity or treatment. Studies of TCR V gene usage in this group of patients may help in understanding the pathogenesis of necrotizing vasculitis, and in the identification of unknown antigens, and may open the possibility to a highly selective immunotherapy by targeting disease-mediating T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal
  • Antibody Specificity
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / physiology
  • Female
  • Granulomatosis with Polyangiitis / blood
  • Granulomatosis with Polyangiitis / genetics*
  • HLA-DR Antigens / physiology
  • Humans
  • Longitudinal Studies
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Polyarteritis Nodosa / blood
  • Polyarteritis Nodosa / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / physiology

Substances

  • Antibodies, Monoclonal
  • HLA-DR Antigens
  • Receptors, Antigen, T-Cell, alpha-beta