Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis.

Objectives To explore the role of V delta 2 T cells in the pathogenesis of rheumatoid arthritis (RA). Methods Sixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral V delta 2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of V delta 2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 on V delta 2 T migration was determined by flow cytometry and transwell migration assay. Results Peripheral V delta 2T cells, but not Vd1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. V delta 2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-gamma and IL-17. Phenotypically, V delta 2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-alpha through nuclear factor kappa B signalling. In vivo, TNF-alpha neutralising therapy dramatically downregulated CCR5 and CXCR3 on V delta 2 T cells and repopulated the peripheral V delta 2 T cells in patients with RA. Conclusions High levels of TNF-a promoted CCR5 and CXCR3 expression in V delta 2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting V delta 2 T cells might be a potential approach for RA.