Peripheral blood T lymphocytes in systemic vasculitis: increased T cell receptor Vβ2 gene usage in microscopic polyarteritis

Abstract

SUMMARY Antigen recognition by T lymphocytes is mediated by cell surface receptors. T cell specificity depends on the variable, diversity and junctional (VDJ) regions of the α and β polypeptide chains of the T cell receptor (TCR). The expression of the variable region genes of the β chain (Vβ) has been analysed to study the involvement of peripheral blood T cells in systemic vasculitis. RNA was extracted from peripheral blood lymphocytes of 12 patients with microscopic polyarteritis, 10 with Wegener's granulomatosis, six with unclassified vasculitis, and 28 healthy age- and sex-matched individuals. Complementary DNA was made from RNA and amplified by the anchored polymerase chain reaction (PCR) using redundant oligonucleotide primers for the TCR Vβ genes. To determine if the dominant usage of a Vβ gene family reflected the presence of particular T cell clones, cDNA was amplified with primers for the specific Vβ gene family. The product was screened for sequence homogeneity by single-stranded conformational polymorphism (SSCP) and cloned to sequence the adjoining TCR (Dβ)Jβ region. A significant increase in the mean percentage expression of the Vβ 2.1 gene was seen in vasculitis patients (11·4+1·0% (mean + s.e.m.)) compared with controls (6·6 + 0·6%; P < 0·003). The most marked increase was seen in microscopic polyarteritis (13·9 + 1·7%; P < 0·0001). There were also increases in the expression of Vβ3, 13 and 14 in peripheral blood of vasculitis patients compared with controls. SSCP analysis of Vβ 2.1 amplified products indicated the presence of oligoclonal bands in a smaller proportion of patients (8/27) than controls (12/28). There was no strong evidence for the conservation of the TCR Vβ 2.1 junctional region sequence data from a sample group of three patients with oligoclonal bands. Thus, a subset of patients with systemic vasculitis, particularly those with microscopic polyarteritis, have increased TCR Vβ 2.1 gene expression in their peripheral blood T cell repertoire. As superantigens binding Vβ 2.1 are postulated to activate T cells with diverse CDR3 sequences, it is proposed that a superantigen is involved in the immunopathogenesis of vasculitis.