Negera Edessa, Bobosha Kidist, Walker Stephen L, Endale Birtukan, Howe Rawleigh, Aseffa Abraham, Dockrell Hazel M, Lockwood Diana N
London School of Hygiene and Tropical Medicine, Faculty of Infectious Diseases, London, United Kingdom.
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Front Immunol. 2017 Sep 15;8:1149. doi: 10.3389/fimmu.2017.01149. eCollection 2017.
Memory T-cells, particularly, effector memory T cells are implicated in the pathogenesis of inflammatory diseases and may contribute to tissue injury and disease progression. Although erythema nodosum leprosum (ENL) is an inflammatory complication of leprosy, the role of memory T cell subsets has never been studied in this patient group. The aim of this study was at investigate the kinetics of memory T cell subsets in patients with ENL before and after prednisolone treatment. A case-control study design was used to recruit 35 untreated patients with ENL and 25 non-reactional lepromatous leprosy (LL) patient controls at ALERT Hospital, Ethiopia. Venous blood samples were obtained before, during, and after treatment from each patient. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of T cell activation and memory T-cell subsets by flow cytometry. The kinetics of these immune cells in patients with ENL before and after treatment were compared with LL patient controls as well as within ENL cases at different time points. The median percentage of CD3, CD4, and CD8 T-cells expressing activated T-cells were significantly higher in the PBMCs from patients with ENL than from LL patient controls before treatment. The median percentage of central and activated memory T-cells was significantly increased in patients with ENL compared to LL patient controls before treatment. Interestingly, patients with ENL had a lower percentage of naïve T cells (27.7%) compared to LL patient controls (59.5%) ( < 0.0001) before treatment. However, after prednisolone treatment, patients with ENL had a higher median percentage of naïve T-cells (43.0%) than LL controls (33.0%) ( < 0.001). The median percentage of activated T-cells (effector memory and effector T-cells) was significantly increased in patients with ENL (59.2%) before treatment compared to after treatment with prednisolone (33.9%) ( < 0.005). This is the first work which has shown T-cell activation and the different subsets of memory T cells in untreated patients with ENL. Consequently, this study delineates the role of T-cell activation in the pathogenesis of ENL reaction and challenges the long-standing dogma of immune complex as a sole etiology of ENL reaction.
记忆T细胞，尤其是效应记忆T细胞，与炎症性疾病的发病机制有关，可能导致组织损伤和疾病进展。虽然结节性红斑（ENL）是麻风病的一种炎症并发症，但记忆T细胞亚群在该患者群体中的作用从未被研究过。本研究的目的是调查泼尼松龙治疗前后ENL患者记忆T细胞亚群的动力学变化。采用病例对照研究设计，在埃塞俄比亚的ALERT医院招募了35例未经治疗的ENL患者和25例无反应性瘤型麻风（LL）患者作为对照。在治疗前、治疗期间和治疗后采集每位患者的静脉血样本。分离外周血单核细胞（PBMC），并通过流式细胞术用于T细胞活化和记忆T细胞亚群的免疫表型分析。将ENL患者治疗前后这些免疫细胞的动力学变化与LL患者对照以及不同时间点的ENL病例进行比较。治疗前，ENL患者PBMC中表达活化T细胞的CD3、CD4和CD8 T细胞的中位数百分比显著高于LL患者对照。与LL患者对照相比，治疗前ENL患者中中央记忆T细胞和活化记忆T细胞的中位数百分比显著增加。有趣的是，治疗前ENL患者的初始T细胞百分比（27.7%）低于LL患者对照（59.5%）（<0.0001）。然而，泼尼松龙治疗后，ENL患者的初始T细胞中位数百分比（43.0%）高于LL对照（33.0%）（<0.001）。与泼尼松龙治疗后（33.9%）相比，治疗前ENL患者中活化T细胞（效应记忆T细胞和效应T细胞）的中位数百分比显著增加（59.2%）（<0.005）。这是第一项显示未经治疗的ENL患者T细胞活化和记忆T细胞不同亚群的研究。因此，本研究阐明了T细胞活化在ENL反应发病机制中的作用，并挑战了免疫复合物作为ENL反应唯一病因的长期教条。
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