LIMITED HETEROGENEITY OF T-CELL RECEPTOR VARIABLE REGION GENE USAGE IN JUVENILE RHEUMATOID-ARTHRITIS SYNOVIAL T-CELLS

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 > 0.003). The TcR V(beta) gene usage by IL-2R+ T cells was even less heterogeneous when compared with freshly isolated SF T cells (p > 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.