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Hyperactivation and enhanced cytotoxicity of reduced CD8+ gamma delta T cells in the intestine of patients with Crohn’s disease correlates with disease activity
BMC Immunology ( IF 3 ) Pub Date : 2024-02-09 , DOI: 10.1186/s12865-024-00606-2
Tao Zhu , Linlin Zhu , Caixia Sheng , Danju Wu , Qianru Gu , Zhinong Jiang , Jiaqi Xu , Guoxiang Fu , Yujie Jiang

We aimed to investigate the immune characteristics of intestinal CD8+ gamma delta T (CD8+ γδ T) cells in Crohn’s disease (CD) and their correlation with disease activity. The study cohorts included 21 CD patients and 21 healthy individuals. CD8+ γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis. The study revealed a reduction in intestinal CD8+ γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8+ γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8+ γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR+ CD8+ γδT cell ratio, CD8+ γδT ratio, and CD8+ γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B+ CD8+ γδT cell and Perforin+ CD8+ γδT cell were identified as indicators that distinguish mildly moderately active CD cases. Intestinal CD8+ γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8+ γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8+ γδ T cells can be used as indicators to assist in diagnosing CD patients.

中文翻译:

克罗恩病患者肠道中 CD8+ γ δ T 细胞减少的过度激活和细胞毒性增强与疾病活动相关

我们的目的是研究克罗恩病 (CD) 中肠道 CD8+ γδ T (CD8+ γδ T) 细胞的免疫特征及其与疾病活动的相关性。研究队列包括 21 名 CD 患者和 21 名健康个体。从人回肠粘膜中分离 CD8+ γδ T 细胞,用于流式细胞术检测。通过检测细胞上激活标志物HLA-DR和免疫抑制分子PD-1的表达来检测细胞的激活或抑制状态。通过检测细胞中细胞毒性分子(穿孔素、颗粒酶B和TRAIL)的表达来评估细胞的细胞毒性。通过接受者操作特征曲线(ROC)分析计算所研究细胞的比率作为预测因子。研究显示,活动性 CD 患者肠道 CD8+ γδT 细胞减少,与轻度活动性患者相比,中度活动性患者的肠道 CD8+ γδT 细胞减少更为明显。此外,活动性 CD 患者肠道 CD8+ γδT 细胞的激活水平较高,而中度活动患者的激活水平相对轻度活动患者较弱。此外,肠道 CD8+ γδT 细胞的细胞毒性仅在轻度活动患者中增强,而与轻度活动患者相比,中度活动患者中肠道 CD8+ γδT 细胞的细胞毒性减弱。此外,HLA-DR+ CD8+ γδT细胞比率、CD8+ γδT比率和CD8+ γδT计数被确定为诊断活动性CD的指标。同时,颗粒酶B+ CD8+ γδT细胞和穿孔素+ CD8+ γδT细胞的比率被确定为区分轻中度活动性CD病例的指标。活动性 CD 患者肠道 CD8+ γδT 降低,但其活化和细胞毒性增强。然而,随着疾病活动的增加,肠道 CD8+ γδ T 细胞变得功能障碍。在 CD8+ γδ T 细胞的各种表型标记物中观察到的 CD 特异性扰动可用作辅助诊断 CD 患者的指标。
更新日期:2024-02-10
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