Hyperactivation and in situ recruitment of inflammatory Vσ 2 T cells contributes to disease pathogenesis in systemic lupus erythematosus

Abstract

In this study, we measured the proportion of peripheral Vσ 2 T cells as well as the status and chemokine receptor expression profiles in SLE patients and healthy control (HC). In addition, Vσ 2 T cell infiltration in the kidneys of patients with lupus nephritis was examined. The results showed that the percentage of peripheral Vσ 2 T cells in new-onset SLE was decreased, and negatively correlated with the SLE Disease Activity Index score and the severity of proteinuria. These cells had a decreased apoptosis but an increased proliferation, and they showed increased accumulation in SLE kidneys. Moreover, IL-21 production and CD40L, CCR4, CCR7, CCR8, CXCR1 and CX3CR1 expression in Vσ 2 T cells from SLE patients was significantly higher than from HC (p < 0.05), and these factors were downregulated in association with the repopulation of peripheral Vσ 2 T cells in patients who were in remission (p < 0.05). In addition, anti-TCR Vσ 2 antibodies activation significantly upregulated these chemokine receptors on Vσ 2 T cells from HC, and this effect was blocked by inhibitors of PLC-γ1, MAPK/Erk, and PI3K signaling pathways. Our findings demonstrate that the distribution and function status of Vσ 2 T cells from SLE patients are abnormal, and these aberrations may contribute to disease pathogenesis.