National Institute of Immunology, New Delhi, India.
J Gastroenterol Hepatol. 2013 Aug;28(8):1403-9. doi: 10.1111/jgh.12186.
The purpose of this study is to assess whether the decrease in CD8 cells has any role in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we therefore used antigen peptide transporter 1 (TAP1(-/-)) mice that cannot transport major histocompatibility complex class I antigens onto the cell surface resulting in failure of the generation of CD8 cells.
Wild-type C57Bl/6J and TAP1(-/-) mice were fed with 30% fructose solution for 8 weeks. The percentage of CD4, CD8 cells in peripheral blood mononuclear cells, and liver were sorted by fluorescence-activated cell sorting in both control and fructose-treated mice. Bodyweight, histopathological changes, oil red O staining, glucose tolerance test, intraperitoneal insulin tolerance test, serum levels of triglycerides, cholesterol, aspartate aminotransferase, and alanine aminotransferase were also evaluated. Quantitative real-time polymerase chain reaction was performed to determine the expression of specific genes involved in development of fatty changes in the liver.
Chronic consumption of fructose in TAP1(-/-) mice did not develop NAFLD, insulin resistance, or change in level of CD8 cells. Moreover, there was delay in relative expression levels of genes involved in development of NAFLD in fructose-treated TAP1(-/-) mice.
Taken together, the data suggest that TAP1(-/-) -deficient mice displayed reduced levels of CD8 cells that have a vital role in the initiation and propagation of liver inflammation and is a casual role in the beginning of fructose-induced liver damage as well as insulin resistance in mice.
本研究旨在评估 CD8 细胞减少是否在非酒精性脂肪性肝病（NAFLD）的发展中起作用。因此，在本研究中，我们使用了不能将主要组织相容性复合物 I 抗原转运到细胞表面的抗原肽转运蛋白 1（TAP1(-/-)）小鼠，导致 CD8 细胞生成失败。
用 30%果糖溶液喂养野生型 C57Bl/6J 和 TAP1(-/-) 小鼠 8 周。用荧光激活细胞分选术对对照组和果糖处理组的外周血单个核细胞和肝脏中的 CD4、CD8 细胞进行分选。评估体重、组织病理学变化、油红 O 染色、葡萄糖耐量试验、腹腔内胰岛素耐量试验、血清甘油三酯、胆固醇、天冬氨酸转氨酶和丙氨酸转氨酶水平。还进行了定量实时聚合酶链反应，以确定参与肝脏脂肪变化发展的特定基因的表达。
慢性果糖摄入在 TAP1(-/-) 小鼠中未发展为 NAFLD、胰岛素抵抗或 CD8 细胞水平改变。此外，果糖处理的 TAP1(-/-) 小鼠中与 NAFLD 发展相关的基因的相对表达水平延迟。
综上所述，数据表明 TAP1(-/-) 缺陷小鼠的 CD8 细胞水平降低，CD8 细胞在肝脏炎症的启动和传播中起重要作用，是果糖诱导的肝损伤和小鼠胰岛素抵抗的起始的因果作用。
