Mo WX, et al. - The role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA) is investigated in this study. High levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells could be a potential approach for RA.

Methods

• In the study, sixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled.
• The 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA was fulfilled by all the selected patients with RA.
• Peripheral Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were measured by flow cytometry.
• The infiltration of Vδ2 T cells within the synovium was analyzed by immunohistochemistry and flow cytometry.
• The impact of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on Vδ2 T migration was determined by flow cytometry and transwell migration assay.

Results

• Peripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints.
• Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17.
• Phenotypically, Vδ2 T cells from RA exhibited raised chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor κ B signalling.
• In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA.