T Cell Receptor VBeta Gene Bias in Rheumatoid Arthritis

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Abstract

Polymerase chain reaction (PCR) technology was employed to examine peripheral blood and synovial T cells in patients with rheumatoid arthritis (RA) for biased utilization of T cell receptor (TCR) variable region (V) genes.Oligonucleotide primers specific for individual TCR Vbeta gene families were used to amplify TCR gene products in a semiquantitative assay of their relative utilization in unselected T cell populations. 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 simultaneously obtained blood samples. Although heterogeneous patterns of skewed Vbeta utilization were observed, several significant trends emerged. By a number of approaches to data analysis, a statistically significant increase in expression of Vbeta6 and Vbeta15 in synovial T cells was documented. In addition, increased synovial expression of Vbeta14 was found, but only in the synovial fluid samples. Reduced expression of Vbeta1, Vbeta4, Vbeta5.1, Vbeta10, Vbeta16, and Vbeta19 was also observed in synovial T cells. These results indicate that biased Vbeta gene 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. (J. Clin. Invest. 1993. 92:2688-2701.) Key words: polymerase chain reaction. rheumatoid arthritis. synovial T cells. T cell receptor. T cell repertoire

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