非酒精性脂肪性肝病患者外周血恒定自然杀伤T细胞和CD4+/CD8+T细胞活化差异研究*

doi:10.3969/j.issn.1672-5069.2023.01.009

摘要/Abstract

摘要： 目的分析不同非酒精性脂肪性肝病(NAFLD)患者外周血恒定自然杀伤T细胞(iNKT)、CD4⁺和CD8⁺ T细胞活化标记物(CD69、CD25、HLA-DR和NKG2D)的表达差异。方法 2020年1月～2022年7月我院诊治的NAFLD患者64例和同期健康体检者50例,对NAFLD患者行肝穿刺活检,使用流式细胞仪检测外周血iNKT、CD4⁺和CD8⁺T细胞CD69、CD25、HLA-DR和NKG2D表达。结果在64例NAFLD患者中,经组织病理学检查,诊断NAFL 37例和NASH 27例;健康对照者、NAFL和NASH患者健康对照者、NAFL和NASH患者外周血CD69⁺iNKT细胞百分比分别为(10.1±1.7)%、(6.1±1.3)%和(26.7±3.6)%(P<0.05),CD25⁺iNKT细胞百分比分别为(83.0±5.9)%、(94.1±8.0)%和(90.8±7.5)%(P<0.05),HLA-DR⁺iNKT细胞百分比分别为(15.3±1.7)%、(15.8±2.0)%和(22.3±2.0)%(P>0.05),NKG2D⁺iNKT细胞百分比分别为(44.5±3.5)%、(59.7±4.0)%和(71.3±6.0)%(P<0.05);外周血CD69⁺CD4⁺ T细胞百分比分别为(0.7±0.2)%、(0.4±0.1)%和(0.5±0.1)%(P>0.05),CD25⁺CD4⁺ T细胞百分比分别为(1.4±0.6)%、(3.0±1.3)%和(1.5±0.7)%(P>0.05),HLA-DR⁺CD4⁺ T细胞百分比分别为(2.7±0.7)%、(4.1±1.0)%和(3.9±1.0)%(P<0.05),NKG2D⁺CD4⁺ T细胞百分比分别为(1.6±0.5)%、(0.6±0.2)%和(0.9±0.2)%(P<0.05);外周血CD69⁺CD8⁺ T细胞百分比分别为(2.0±0.4)%、(1.6±0.3)%和(2.1±0.6)%(P>0.05),CD25⁺CD8⁺ T细胞百分比分别为(1.3±0.3)%、(1.1±0.2)%和(1.0±0.2)%(P>0.05),HLA-DR⁺CD8⁺ T细胞百分比分别为(5.0±0.7)%、(6.5±1.0)%和(9.6±1.4)%(P<0.05),NKG2D⁺CD8⁺ T细胞百分比分别为(0.6±0.1)%、(0.5±0.1)%和(0.9±0.2)%(P<0.05)。结论本研究发现NAFL与NASH患者可能存在外周血iNKT细胞、CD4⁺和CD8⁺ T细胞活化的免疫表型差异,显示NASH患者CD69⁺iNK T细胞百分比增高,可能对诊断有帮助,值得进一步研究。

关键词: 非酒精性脂肪性肝病, 单纯性脂肪肝, 非酒精性脂肪性肝炎, 恒定自然杀伤T细胞

Abstract: Objective The aim of this study was to investigate the expression of activation markers, such as CD69, CD25, HLA-DR and NKG2D, of peripheral blood invariant natural killer T cells (iNKT), CD4⁺ and CD8⁺ T cells in patients with nonalcoholic fatty liver diseases (NAFLD). Methods 64 patients with NAFLD and 50 healthy persons were enrolled in our hospital between January 2020 and July 2022, and all patients with NAFLD received liver biopsies. The expression of activation markers, such as CD69, CD25, HLA-DR and NKG2D in peripheral blood iNKT, CD4⁺ and CD8⁺ T cells was detected by FCM. Results The liver histopathological examination showed that the nonalcoholic fatty liver (NAFL) was found in 37 cases and nonalcoholic steatohepatitis (NASH) was found in 27 cases; the percentages of peripheral blood CD69⁺iNKT cells in healthy individuals, patients with NAFL and patients with NASH were (10.1±1.7)%,(6.1±1.3)% and (26.7±3.6)%(P<0.05), the percentages of CD25⁺iNKT cells were (83.0±5.9)%, (94.1±8.0)% and (90.8±7.5)%(P<0.05), the percentages of HLA-DR⁺iNKT cells were (15.3±1.7)%, (15.8±2.0)% and (22.3±2.0)%(P>0.05), and the percentages of NKG2D⁺iNKT cells were (44.5±3.5)%, (59.7±4.0)% and (71.3±6.0)%(P<0.05); the percentages of peripheral blood CD69⁺CD4⁺ T cells were (0.7±0.2)%, (0.4±0.1)% and (0.5±0.1)%(P>0.05), the percentages of CD25⁺CD4⁺ T cells were (1.4±0.6)%, (3.0±1.3)% and (1.5±0.7)%(P>0.05), the percentages of HLA-DR⁺CD4⁺ T cells were (2.7±0.7)%, (4.1±1.0)% and (3.9±1.0)%(P<0.05), and the percentages of NKG2D⁺CD4⁺ T cells were (1.6±0.5)%, (0.6±0.2)% and (0.9±0.2)%(P<0.05); the percentages of peripheral blood CD69⁺CD8⁺ T cells in the three groups were (2.0±0.4)%, (1.6±0.3)% and (2.1±0.6)%(P>0.05), the percentages of CD25⁺CD8⁺ T cells were (1.3±0.3)%, (1.1±0.2)% and (1.0±0.2)%(P>0.05), the percentages of HLA-DR⁺CD8⁺ T cells were (5.0±0.7)%, (6.5±1.0)% and (9.6±1.4)%(P<0.05), and the percentages of NKG2D⁺CD8⁺ T cells were (0.6±0.1)%, (0.5±0.1)% and (0.9±0.2)%(P<0.05). Conclusion In this study, we find the immunophenotypic activation differences of peripheral blood iNKT, CD4⁺ and CD8⁺ T cells in patients with NAFL and patients with NASH, and the results show that the percentage of CD69⁺iNK T cells increase in patients with NASH, which might hint the CD69⁺iNK T cells as a biological marker for the diagnosis of patients with NASH.

Key words: Nonalcoholic fatty liver diseases, Nonalcoholic fatty liver, Nonalcoholic steatohepatitis, Invariant natural killer T cells

陈凤莲, 朱青蓝, 朱伶俐, 陈国飞. 非酒精性脂肪性肝病患者外周血恒定自然杀伤T细胞和CD4⁺/CD8⁺T细胞活化差异研究^*[J]. 实用肝脏病杂志, 2023, 26(1): 31-34.

Chen Fenglian, Zhu Qinglan, Zhu Lingli, et al. Different activation of peripheral blood invariant natural killer T cells and CD4⁺/CD8⁺T cells in patients with nonalcoholic fatty liver diseases[J]. Journal of Practical Hepatology, 2023, 26(1): 31-34.

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