DOMINANT T-CELL-RECEPTOR-BETA CHAIN VARIABLE REGION V-BETA-14(+) CLONES IN JUVENILE RHEUMATOID-ARTHRITIS

The characteristic histopathology and major histocompatibility complex associations in juvenile rheumatoid arthritis suggest an oligoclonal antigen-specific T-cell population may be critical to pathogenesis. To test this, we analyzed the T-cell repertoire of a polyarticular HLA-DR4+ juvenile rheumatoid arthritis patient with an aggressive form of disease that required arthrocentesis of the knee joints and early replacement of both hip joints. A comparison of T-cell-receptor beta chain variable region (Vbeta) gene expression in peripheral blood and synovial fluid performed by semiquantitation of cDNA samples amplified by the PCR revealed overexpression of the T-cell-receptor Vbeta14 gene family. To determine the nature of Vbeta14 overexpression, we sequenced randomly cloned amplification products derived from two synovial fluid, two synovial tissue, and three peripheral blood samples by using a Vbeta14/beta chain constant region primer pair. Sequence data showed that the T-cell response in the synovia was oligoclonal. Of four clones found, one was present in all joints examined and persisted over time. This clone accounted for 67% and 74% of all Vbeta14+ clones sequenced in two synovial fluid samples and 75% and 40% in two synovial tissue samples. This clone was also found at a lesser frequency in peripheral blood samples. Further studies provided evidence for the presence of oligoclonally expanded populations of T cells utilizing the Vbeta14 T-cell receptor in 6 of 27 patients examined. In contrast to the remaining patients studied, 3 with a late onset polyarticular course who exhibited especially marked clonality were characterized by features typical of adult rheumatoid arthritis (IgM rheumatoid factor-positive and HLA-DR4+). These data suggest a role for Vbeta14+ T cells in a group of juvenile rheumatoid arthritis patients.