Wang Hongliang, Sun Na, Li Ka, Tian Jiguang, Li Jianmin
Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).
Department of Orthopedics, Shandong Institute of Medicine and Health Information, Jinan, Shandong, China (mainland).
Med Sci Monit. 2016 Sep 6;22:3163-8. doi: 10.12659/msm.897126.
BACKGROUND Ankylosing spondylitis (AS) involves inflammation at the sacroiliac joint and spine attachment site. This study aimed to observe the ratio and function of peripheral regulatory Vδ1 T cells in AS patients to investigate their roles in AS pathogenesis. MATERIAL AND METHODS Peripheral blood mononuclear cells (PBMC) were separated by density-gradient centrifugation from AS patients and healthy controls. Flow cytometry was used to determine the ratio between Vδ1 and CD4 T cells of PBMC in AS patients and controls. Flow cytometry sorting (FCS) was used to obtain Vδ1 and naïve CD4 T cells with purity higher than 90%. CFSE staining method was used to detect the effect of Vδ1 T cells on proliferation of naïve CD4 T cells. The effect of Vδ1 T cells on secretion of IFN-γ from naïve CD4 T cells and the ability to secrete IL-10 from Vδ1 T cells were determined by flow cytometry. RESULTS AS patients had significantly lower Vδ1 T cell ratio in PBMC compared to controls (p<0.05), but their CD4 T cell ratio was significantly elevated (p<0.05). Functional assay showed suppression of naïve CD4 T cell proliferation and IFN-γ secretion by peripheral Vδ1 T cells in AS patients (p<0.01). AS patients also had lower IL-10 secreting level from peripheral derived Vδ1 T cells (p<0.01). CONCLUSIONS The immune suppression of peripheral Vδ1 T cell in AS patient increases the ratio of peripheral CD4 T cells and IFN-γ level, leading to AS pathogenesis. This immune suppression is mainly due to suppressed IL-10 secretion.
强直性脊柱炎(AS)累及骶髂关节和脊柱附着部位的炎症。本研究旨在观察AS患者外周调节性Vδ1 T细胞的比例和功能,以探讨其在AS发病机制中的作用。
通过密度梯度离心法从AS患者和健康对照者中分离外周血单个核细胞(PBMC)。采用流式细胞术测定AS患者和对照者PBMC中Vδ1与CD4 T细胞的比例。采用流式细胞术分选(FCS)获得纯度高于90%的Vδ1和初始CD4 T细胞。采用CFSE染色法检测Vδ1 T细胞对初始CD4 T细胞增殖的影响。通过流式细胞术测定Vδ1 T细胞对初始CD4 T细胞分泌IFN-γ的影响以及Vδ1 T细胞分泌IL-10的能力。
与对照组相比,AS患者PBMC中Vδ1 T细胞比例显著降低(p<0.05),但其CD4 T细胞比例显著升高(p<0.05)。功能分析显示,AS患者外周Vδ1 T细胞抑制初始CD4 T细胞增殖和IFN-γ分泌(p<0.01)。AS患者外周来源的Vδ1 T细胞分泌IL-10的水平也较低(p<0.01)。
AS患者外周Vδ1 T细胞的免疫抑制增加了外周CD4 T细胞比例和IFN-γ水平,导致AS发病。这种免疫抑制主要是由于IL-10分泌受抑制。