T cell receptor (TCR) V gene usage in patients with systemic necrotizing vasculitis.
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.
Giscombe
R
R
Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Grunewald
J
J
Nityanand
S
S
Lefvert
A K
AK
D000368:Aged; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000235:genetics*; D006684:HLA-DR Antigens / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010488:Polyarteritis Nodosa / Q000097:blood / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000502:physiology
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta