Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Pathology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Pancreatology. 2023 Nov;23(7):767-776. doi: 10.1016/j.pan.2023.08.005. Epub 2023 Aug 28.
IgG4-related autoimmune pancreatitis (AIP) is considered to be a T cell-mediated autoimmune disease. However, CD8 T cells have only received brief mention, and have yet to be completely studied. The study aimed to investigate the expression of signaling lymphocytic activation molecule family 7 (SLAMF7) on CD8 T cells and the features of SLAMF7CD8 T cells in MRL/Mp mice with AIP.
A murine model of AIP was established by intraperitoneal injection with polyinosinic:polycytidylic acid (poly I:C) for 8 weeks. Dexamethasone treatment was daily administrated for the last 2 weeks during a 6-week course of poly I:C. SLAMF7 expression on CD8 T cells in the spleen and pancreas was detected by flow cytometry. Granzyme B (GZMB) and cytokines including IFN-γ, TNF-α, and IL-2, were monitored in an in vitro T cell activation assay. Dexamethasone suppression assays were performed to downregulate SLAMF7 expression on T cells upon T cell receptor stimulation.
AIP in MRL/Mp mice was induced by repeated intraperitoneal administration of poly I:C and CD8 T cells were increased in the inflamed pancreas. SLAMF7CD8 T cells were elevated in the spleen and pancreas of AIP mice. SLAMF7CD8 T subsets produced more GZMB, IFN-γ, TNF-α and IL-2 than SLAMF7CD8 T subsets. Dexamethasone treatment ameliorated pancreatic inflammatory and fibrosis of AIP. Dexamethasone could downregulate SLAMF7CD8 T cells and reduce GZMB, IFN-γ and TNF-α levels both in vitro and in vivo.
Increased SLAMF7CD8 T cells exhibit enhanced cytotoxicity and cytokines secretion capacity, which may be involved in the pathogenesis of AIP.
IgG4 相关自身免疫性胰腺炎（AIP）被认为是一种 T 细胞介导的自身免疫性疾病。然而，CD8 T 细胞仅被简要提及，尚未得到全面研究。本研究旨在探讨信号淋巴细胞激活分子家族 7（SLAMF7）在 AIP 模型鼠 MRL/Mp 小鼠 CD8 T 细胞上的表达及其特征。
采用腹腔注射聚肌胞苷酸（poly I:C）的方法建立 AIP 模型鼠，在 6 周 poly I:C 注射周期的最后 2 周给予地塞米松治疗。采用流式细胞术检测脾和胰腺中 CD8 T 细胞上 SLAMF7 的表达。在体外 T 细胞激活实验中监测颗粒酶 B（GZMB）和包括 IFN-γ、TNF-α 和 IL-2 在内的细胞因子。采用地塞米松抑制实验下调 T 细胞受体刺激时 T 细胞上的 SLAMF7 表达。
通过反复腹腔内给予 poly I:C 诱导 MRL/Mp 小鼠发生 AIP，且在炎症胰腺中 CD8 T 细胞增加。AIP 小鼠的脾和胰腺中 SLAMF7CD8 T 细胞增加。与 SLAMF7CD8 T 细胞亚群相比，SLAMF7CD8 T 细胞亚群产生更多的 GZMB、IFN-γ、TNF-α 和 IL-2。地塞米松治疗可改善 AIP 的胰腺炎症和纤维化。地塞米松可下调 SLAMF7CD8 T 细胞，并在体外和体内降低 GZMB、IFN-γ 和 TNF-α 水平。
SLAMF7CD8 T 细胞增加，其细胞毒性和细胞因子分泌能力增强，这可能与 AIP 的发病机制有关。
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