Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid arthritis synovial T cells

Abstract

The aim of this study was to determine whether synovial fluid (SF) T cells in patients with juvenile rheumatoid arthritis (JRA) are restricted in their T cell receptor (TcR) gene repertoire. The quantitative polymerase chain reaction (QPCR) was used to compare the transcription of V beta and V alpha gene families in freshly isolated SF T cells, in interleukin-2 receptor-positive (IL-2R+) T cells and in peripheral blood (PB) T cells from 18 patients. Significantly less V beta families are detected in SF when compared with PB (p greater than 0.0003). The TcR V beta gene usage by IL-2R+ T cells was even less heterogeneous when compared with freshly isolated SF T cells (p greater than 0.0002). Freshly isolated SF T cells from the left and the right knees of four patients transcribed the same V beta families. Furthermore, we demonstrate that in SF the distribution of certain TcR V beta gene segments in CD4+ and CD8+ T cells differed from that in PB of the same patient. The TcR V alpha usage was studied in IL-2R+ T cells from six patients who had shown restriction in their SF TcR V beta gene usage. Only two to five TcR alpha transcripts were detected in three of these patients while a broad TcR V alpha usage was seen in the other three patients. Sequence analysis of the SF V beta 20 cDNA clones generated from the IL-2R+ T cells of two patients demonstrated an oligoclonal expansion. Taken together, our data could indicate an antigen- and/or superantigen-driven expansion of selected T cells in the synovial compartment.