T-CELL RECEPTOR V-BETA GENE BIAS IN RHEUMATOID-ARTHRITIS

Polymerase chain reaction (PCR) technology was employed to examine per ipheral blood and synovial T cells in patients with rheumatoid arthrit is (RA) for biased utilization of T cell receptor (TCR) variable regio n (V) genes. Oligonucleotide primers specific for individual TCR Vbeta gene families were used to amplify TCR gene products in a semiquantit ative assay of their relative utilization in unselected T cell populat ions. Mean Vbeta expression in 24 RA peripheral blood samples was very similar to that in a panel of 15 normal subjects, except for a slight decrease in Vbeta13.2 expression. Vbeta utilization in 8 RA synovial tissue samples and 13 synovial fluid samples was compared to simultane ously obtained blood samples. Although heterogeneous patterns of skewe d Vbeta utilization were observed, several significant trends emerged. By a number of approaches to data analysis, a statistically significa nt increase in expression of Vbeta6 and Vbeta15 in synovial T cells wa s documented. In addition, increased synovial expression of Vbeta14 wa s found, but only in the synovial fluid samples. Reduced expression of Vbeta1, Vbeta4, Vbeta5.1, Vbeta10, Vbeta16, and Vbeta19 was also obse rved in synovial T cells. These results indicate that biased Vbeta gen e utilization in different peripheral compartments of RA patients can be observed in unselected T cell populations, and are consistent with the conclusion that populations of T cells expressing these Vbeta gene products may be involved in the pathogenesis of the disease.