High expression of Vγ8 is a shared feature of human γδ T cells in the epithelium of the gut and in the inflamed synovial tissue

We have analyzed the V-gene usage in γδ T cells of the human gut and joint by using a new mAb (B18) specific for Vγ8 of human TCR-γδ⁺ T cells. The B18⁺ population constituted a minor subset of the γδ T cells in peripheral blood (PB) of healthy persons (6 ± 5%) and only 1 of 35 γδ T cell clones analyzed was positive. In contrast, the B18⁺ subset was a dominant γδ T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 ± 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18⁺. Interestingly, a higher proportion of B18⁺ γδ T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 ± 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18⁺ subset was more frequent among IL-2- expanded γδ T cells (42 ± 20%) derived from synovial tissue than among IL- 2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 γδ T cell clones from the synovial fluid of arthritic patients was analyzed. All B18⁺ clones (n = 7) expressed mRNA for Vγ8 together with mRNA for Vδ1 (n = 5) or mRNA for Vδ3 (n = 2). None of the B18^- clones expressed Vγ8 (n = 6). We conclude that the γδ T cell that expresses Vγ8, together with mainly Vδ1, is a major γδ T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse Vγ7⁺ IEL, which has a high degree of amino acid sequence homology with the human Vγ8 protein.