Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements

Abstract

Clonally expanded, autoreactive CD4(+)CD28(null) cells can be found in the peripheral blood of patients with rheumatoid arthritis and have been shown to be associated with severeextra-articular disease manifestations. We investigated the size of the CD4(+)CD28(null) compartment and the TCR beta chain repertoire of expanded CD4(+) clonotypes in 94 rheumatoid arthritis patients by complementarity-determining region 3 (CDR3) length analysis (spectratyping) in the BV6 and BV14 TCR families, with primers specific for three arbitrarily chosen beta chain joining elements (BJ1S2, BJ2S3 and BJ2S7). The spectratyping results showed a strong correlation of the size of the CD4(+)CD28(null) compartment with the detected number of BV14 clonotypes, whereas no association with BV6 oligoclonality was found. Only clones using the BV14-BJ1S2 and BV14-BJ2S3 combinations contributed to this correlation, however, whereas BV14-BJ2S7 clones did not. This preferential correlation implies a role for the TCR beta chain in stimulating clonal outgrowth and argues against the previously suggested superantigenic stimulation of in-vivo-expanded clones. Instead, since no evidence for shared antigen specificity could be detected, clonal expansion of T cells in rheumatoid arthritis might be influenced by the BJ elements because of changes in the flexibility of the protein backbone of the beta-chain.