Selective expansion of large lymphoblasts expressing Vβ6.1-3 or 7 in synovial fluid from patients with rheumatoid arthritis

Abstract

The affected joints of patients with rheumatoid arthritis (RA) contain a large number of T cells, of which those expressing specific T cell receptor (TCR) Vβ chains are thought to play an important role in the pathogenesis of RA. The TCR Vβ repertoire of large lymphoblasts and small non-blasts from the synovial fluid (SF) and peripheral blood (PB) of RA patients, as well as their responsiveness to staphylococcal enterotoxin A (SEA), was investigated. TCR Vβ repertoire was examined with a semiquantitative reverse transcription-polymerase chain reaction assay, as was expression of genes encoding interleukin (IL)-2 and IL-4. Production of IL-2 and IL-4 was measured with a bioassay and an enzyme immunoassay system, respectively. Expression of TCR Vβ6.1-3, 7 and 15 was more frequent among large lymphoblasts than among small non-blasts in paired preparations from the 14 SF of 14 RA patients. TCR Vβ7 was expressed more frequently by large lymphoblasts than by small non-blasts in the PB of eight RA patients. The usage of TCR Vβ6.1-3 and 7 by large lymphoblasts in SF from RA patients significantly reduced in response to SEA stimulation. Both IL-2 production and gene expression as well as IL-4 production and gene expression in large lymphoblasts from the SF of RA patients increased to a lesser extent in response to SEA stimulation compared with the effects observed in paired small non-blasts. In summary, large lymphoblasts expressing TCR Vβ6.1-3, 7 and 15 were selectively expanded in SF of RA patients, and those bearing TCR Vβ6.1-3 or 7 were selectively unresponsive to SEA stimulation. These results indicate that SF lymphoblasts bearing Vβ6.1-3 or 7 were anergic with regard to stimulation with superantigen, suggesting the implication of a superantigen in previous activation of T cells in SF of RA patients.