Department of Pathology, Sir Run Run Shaw Hospital Affiliated with Zhejiang University School of Medicine, Hangzhou, 310000, China.
Department of Gastroenterology, Sir Run Run Shaw Hospital Affiliated with Zhejiang University School of Medicine, Hangzhou, 310000, China.
BMC Immunol. 2024 Feb 9;25(1):15. doi: 10.1186/s12865-024-00606-2.
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.
本研究旨在探讨克罗恩病（CD）患者肠道 CD8γδT（CD8γδT）细胞的免疫特征及其与疾病活动度的相关性。
研究队列包括 21 例 CD 患者和 21 例健康对照者。采用流式细胞术检测人回肠黏膜中 CD8γδT 细胞。通过检测细胞表面活化标志物 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。通过受试者工作特征曲线（ROC）分析计算各细胞比例作为预测因子。
研究发现，活动期 CD 患者肠道 CD8γδT 细胞减少，中度活动期患者较轻度活动期患者减少更为明显。此外，活动期 CD 患者肠道 CD8γδT 细胞的活化水平升高，而中度活动期患者的活化水平较轻度活动期患者减弱。此外，仅轻度活动期患者肠道 CD8γδT 细胞的细胞毒性增强，而中度活动期患者的细胞毒性较轻度活动期患者受损。此外，HLA-DR CD8γδT 细胞比例、CD8γδT 比例和 CD8γδT 计数可作为诊断活动期 CD 的指标。同时，Granzyme B CD8γδT 细胞和 Perforin CD8γδT 细胞的比例可作为区分轻度和中度活动期 CD 的指标。
活动期 CD 患者肠道 CD8γδT 细胞减少，但它们的激活和细胞毒性增强。然而，随着疾病活动度的增加，肠道 CD8γδT 细胞功能失调。CD8γδT 细胞中各种表型标志物的 CD 特异性改变可作为辅助诊断 CD 患者的指标。
