SELECTIVE ACCUMULATION OF RELATED CD4(-CELL CLONES IN THE SYNOVIAL-FLUID OF PATIENTS WITH RHEUMATOID-ARTHRITIS() T)

The role of T cells in the pathogenesis of rheumatoid arthritis (RA), especially in the perpetuation of advanced disease, remains unclear, P revious studies have focused on the TCR repertoire of synovial T cells in an attempt to determine whether the pattern of expression is chara cteristic of Ag-stimulated populations, However, the results of past s tudies have been conflicting. In the present work, we have undertaken an extensive analysis of the TCRs expressed by CD4(+) T cells freshly isolated from synovial fluid of different joints and blood in three pa tients with established RA, Despite marked heterogeneity of synovial T CR expression, the results showed that 20 to 30% of the TCR beta-chain gene (TCRB) sequences found in one joint were also expressed in a sec ond joint, but not ire peripheral blood T cells of the same individual . Analysis of expressed TCRB complementarity-determining region 3 sequ ences showed the presence of multiple expanded clonal populations that were not predicted by quantitation of beta-chain variable region (V b eta) expression by immunofluorescence staining. These studies also dem onstrated sets of related, but different, complementarity-determining region 3 nucleotide sequences that encoded identical or highly homolog ous beta-chain amino acid sequences, analysis of matching T cell clone s derived from the joint by limiting dilution culture confirmed coexpr ession of highly homologous TCR alpha-chain gene (TCRA) and TCRB seque nces. Together, these studies suggest that a significant proportion of synovial CD4(+) T cells has beers selected and expanded by convention al Ag(s) in this disease.