目的:人γδT细胞(γδ-T细胞)在先天免疫和适应性免疫反应中起着至关重要的作用。然而,关于系统性红斑狼疮(SLE)患者γδT细胞的免疫状态知之甚少。这项研究的目的是探索γδ-T细胞亚群的频率与疾病活动之间的潜在关系。SLE患者的自身抗体滴度和肾脏受累。
方法:循环γδ-T细胞及其亚群(Vδ1+T细胞,由表面受体表达定义的Vδ2+T细胞和γδ-T细胞亚群,包括NKG2D,NKp30、NKp46和PD-1),通过流式细胞术鉴定。选择60例活动性SLE患者,包括41例新发病例和19例复发病例。100名健康对照(HC)作为对照组。分析了SLE患者和HCs中这些细胞亚群的百分比及其与疾病活动的关系。41例新发SLE患者中的22例在治疗前后进行了评估。还分析了这些细胞亚群的频率变化及其与肾脏受累的关系。
结果:与HC相比,SLE患者中总γδ-T细胞在CD3+T细胞中的百分比显著降低。观察到γδ-T细胞中Vδ1和Vδ2T细胞的比例不平衡。SLE患者的γδ-T细胞中Vδ1+T细胞的比例明显高于HCs,而Vδ2+T细胞的比例明显降低。PD-1、NKG2D、SLE患者的Vδ1+T细胞和Vδ2+T细胞中NKp30和NKp46普遍显著增高,除了NKG2D在Vδ2+T细胞中的表达。此外,Vδ2+T细胞,Vδ1+T细胞和Vδ1+PD-1+T细胞与疾病活动有关,Vδ2+T细胞频率的增加和γδ-T细胞表达的减少可能与有效治疗有关。有趣的是,我们的结果表明,Vδ2T细胞及其Vδ2NKp30T细胞亚群可能与SLE的肾脏受累有关。
结论:SLE患者中γδ-T细胞亚群和γδ-T细胞比例的广泛异常可能与SLE的发病有关。Vδ2+T细胞与其Vδ2+NKp30+T细胞亚群和LN发生之间存在很强的关联。我们的结果表明,γδ-T细胞及其亚群可能是SLE疾病免疫病理学和肾脏受累的关键参与者。
OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE.
METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed.
RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE.
CONCLUSIONS: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.