1 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, China .
2 Shaanxi Provincial Engineering Research Center of Biotherapy and Translational Medicine, and The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, Shaanxi Province, China .
J Interferon Cytokine Res. 2019 Feb;39(2):95-105. doi: 10.1089/jir.2018.0121. Epub 2019 Jan 24.
Our study aimed to investigate the histologic and immunological changes of portal hypertension (PH) pre- and postsplenectomy in hepatitis B virus (HBV)-related cirrhosis. Peripheral blood samples were obtained from 30 patients with HBV-related cirrhosis and PH at pre- and postsplenectomy time points and from 15 healthy subjects. Spleen tissue specimens were collected from 15 of the patients with HBV-related cirrhosis and from 8 control patients who had undergone splenectomy due to trauma. Immunohistochemical staining was performed to evaluate the immune effector cells and the expression of negative immune regulators. Flow cytometry was used to investigate the immunophenotypes and percentages. The spleen of cirrhotic patients with PH showed extensive depletion of splenic CD4, CD8, and human leukocyte antigen DR cells along with overexpression of the inhibitory receptors programmed death-1 (PD-1) and T cell immunoglobulin domain and mucin domain-3 and their ligands (PD-L2 and galectin-9). Peripheral blood of patients with PH showed remarkable decrease in proportions of CD8 T cell and natural killer (NK) cells and increase in regulatory T (Treg) cells, as well as high expression of PD-1 in CD4/8 T cells. Compared with presplenectomy patients, cirrhotic patients with PH showed increased proportions of CD8 and NK cells, decreased proportion of Treg cells, and decreased expression of PD-1 in peripheral blood CD4/8 T cells after splenectomy. PH-spleen could lead to peripheral tolerance and immunosuppression in HBV cirrhotic patients, and splenectomy may cause beneficial immunological changes.
我们的研究旨在探讨乙型肝炎病毒（HBV）相关肝硬化患者脾切除术前和术后门静脉高压（PH）的组织学和免疫学变化。在脾切除术前和术后，从 30 例 HBV 相关肝硬化伴 PH 的患者和 15 例健康对照者中获得外周血样本。从 15 例 HBV 相关肝硬化患者和 8 例因外伤行脾切除术的对照患者中收集脾组织标本。进行免疫组织化学染色以评估免疫效应细胞和负性免疫调节剂的表达。流式细胞术用于研究免疫表型和百分比。PH 肝硬化患者的脾脏显示广泛的 CD4、CD8 和人类白细胞抗原 DR 细胞耗竭，同时程序性死亡-1（PD-1）和 T 细胞免疫球蛋白域和粘蛋白域-3 及其配体（PD-L2 和半乳糖凝集素-9）的抑制性受体过度表达。PH 患者的外周血显示 CD8 T 细胞和自然杀伤（NK）细胞比例显著降低，调节性 T（Treg）细胞比例增加，以及 CD4/8 T 细胞中 PD-1 高表达。与脾切除术前患者相比，PH 肝硬化患者脾切除术后外周血 CD4/8 T 细胞中 CD8 和 NK 细胞比例增加，Treg 细胞比例降低，PD-1 表达降低。PH 脾可能导致 HBV 肝硬化患者外周耐受和免疫抑制，脾切除术可能引起有益的免疫变化。
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