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结核患者 T 细胞亚群中白细胞介素-7 受体表达减少。

Diminished Interleukin-7 receptor expression on T-cell subsets in tuberculosis patients.

机构信息

Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.

Agogo Presbyterian Hospital, Agogo, Ghana.

出版信息

Hum Immunol. 2023 Oct;84(10):543-550. doi: 10.1016/j.humimm.2023.08.141. Epub 2023 Aug 12.

Abstract

Immunopathology in human tuberculosis affects T-cell phenotype and functions. Previous studies identified impaired T-cell sensitivity to Interleukin (IL)-7 accompanied by lower IL-7 receptor α-chain (IL-7Rα) expression in patients with acute tuberculosis. In the present study, we characterized affected T-cell subsets and determined the influence of tuberculosis disease severity and treatment response. Tuberculosis patients (n = 89) as well as age- and gender-matched asymptomatic contacts (controls, n = 47) were recruited in Ghana. Mycobacterium (M.) tuberculosis sputum burden was monitored prior to and during treatment. Blood samples from all patients and controls were analyzed for IL-7Rα expression and T-cell markers by multi-colour flow cytometry. CD4 and CD8 T-cells of tuberculosis patients showed generally lower IL-7Rα expression as compared to controls. Concomitantly, tuberculosis patients had higher proportions of naïve and lower proportions of memory CD4 T-cells. Notably, a subset of CD27 positive central memory T-cells (T), which lacked IL-7Rα expression was enriched in tuberculosis patients as compared to controls. M. tuberculosis sputum burden was not associated with differences in IL-7Rα expression. Treatment duration and response showed no clear effects although IL-7Rα expression patterns were highly variable. These results suggested generally impaired generation of memory CD4 T-cells and enrichment of a T subset without IL-7Rα expression in patients with tuberculosis.

摘要

人类结核病的免疫病理学影响 T 细胞表型和功能。先前的研究表明,急性结核病患者的 T 细胞对白细胞介素(IL)-7 的敏感性降低,同时伴有 IL-7 受体α链(IL-7Rα)表达降低。在本研究中,我们对受影响的 T 细胞亚群进行了特征描述,并确定了结核病严重程度和治疗反应的影响。在加纳招募了 89 名结核病患者(n=89)和年龄及性别匹配的无症状接触者(对照组,n=47)。在治疗前和治疗期间监测分枝杆菌(M.)结核分枝杆菌痰负荷。对所有患者和对照者的血液样本进行 IL-7Rα表达和 T 细胞标志物的多色流式细胞术分析。与对照组相比,结核病患者的 CD4 和 CD8 T 细胞的 IL-7Rα表达普遍较低。同时,结核病患者的幼稚 CD4 T 细胞比例较高,记忆 CD4 T 细胞比例较低。值得注意的是,与对照组相比,结核病患者中缺乏 IL-7Rα表达的 CD27 阳性中央记忆 T 细胞(T)亚群明显富集。M. tuberculosis 痰负荷与 IL-7Rα表达的差异无关。虽然 IL-7Rα表达模式高度可变,但治疗持续时间和反应没有明显影响。这些结果表明,结核病患者的记忆性 CD4 T 细胞生成普遍受损,并且缺乏 IL-7Rα表达的 T 细胞亚群富集。

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