Hospital Nacional de Clínicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Universidad Nacional de Córdoba and Consejo Nacional de Investigaciones Científicas y Técnicas, Córdoba, Argentina.
Arthritis Rheumatol. 2018 Sep;70(9):1429-1439. doi: 10.1002/art.40521. Epub 2018 Aug 6.
Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor-mediated pathways were functional.
Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined.
In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor-expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition.
Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.
抑制性受体对于效应免疫反应的调节至关重要，并且可能在自身免疫性疾病中发挥关键作用。我们评估了类风湿关节炎（RA）患者 T 细胞上的抑制性受体表达与免疫激活、疾病活动度和治疗反应的相关性，以及抑制性受体介导的途径是否具有功能。
我们使用流式细胞术对 RA 患者血液和滑液（SF）中的 CD4+和 CD8+T 细胞进行了广泛的表型和功能评估，包括体外和培养后的评估。我们还检查了每个参数与红细胞沉降率（DAS28-ESR）的 28 个关节疾病活动度评分（DAS28-ESR）和治疗反应之间的关系。
在 T 细胞活化水平较低的 RA 患者中，抑制性受体表达与 DAS28-ESR 呈负相关。未接受治疗的 RA 患者中表达多种抑制性受体的 T 细胞频率降低，但在接受治疗的患者中恢复正常水平。与无应答者相比，对治疗有反应的 RA 患者表现出表达抑制性受体的 T 细胞频率增加，并且与炎症细胞因子产生减少相关。与外周血相比，SF 中表达多种抑制性受体的效应和记忆 T 细胞频率更高。值得注意的是，所有 RA 患者的血液和滑膜 T 细胞中都存在抑制性途径，但无应答患者的细胞对抑制作用的敏感性较低。
RA 患者 T 细胞上的抑制性受体表达与效应 T 细胞功能和疾病活动度呈负相关，并且可能预测治疗反应。此外，不同的抑制性途径具有功能并且协同抑制滑膜 T 细胞，为调节急性局部炎症的新治疗策略提供了依据。
