The biased Vγ gene usage in the synovial fluid of patients with rheumatoid arthritis

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Abstract
Taking advantage of the reverse transcriptase-polymerase chain reaction (RT-PCR), we have analyzed T cell receptor γ-chain mRNA of synovial fluid γ/δ T cells from patients with rheumatoid arthritis (RA) in comparison with those of peripheral blood mononuclear cells (PBMC) from RA patients and healthy individuals. The quantitative RT-PCR method in conjunction with nucleotide sequencing revealed the frequent usage of the Vγ3 gene segment in RA synovial fluid mononuclear cells (SFMC) (p < 0.01) which in PBMC of healthy individuals occurred rarely. PBMC of most healthy individuals expressed the Vγ9 gene predominantly (p < 0.01) as expected. However, only half of RA patients showed elevated levels of the Vγ9 gene expression in their PBMC. The γ-chain mRNA containing the Vγ3 gene in RA SFMC showed no conserved junctional sequence (complementarity-determining region 3). To investigate the nature of ligands recognized by the Vγ3-bearing T cells, we analyzed Vγ gene usage of RA SFMC, RA PBMC, and normal PBMC stimulated with Mycobacterium tuberculosis (MT) or MT plus interleukin-2 since there is mounting evidence of high reactivity of RA SFMC to MT and mycobacterial heat-shock protein 65. However, the Vγ usage appeared to be mostly Vγ9 in RA SFMC, RA PBMC and normal PBMC. Taken together these results suggest that an as yet unknown antigen(s) (other than MT) might select γ/δ T cells expressing the Vγ3 gene in RA SFMC.