AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection wer...AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total T cells was detected by flow cytometry.Levels of total CD8+T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULTS:The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.展开更多
目的通过应用孟德尔随机化(Mendelian randomization,MR)方法,系统探究10种尿毒症相关毒素及代谢物与CD8^(+)T细胞衰老表型之间的双向因果关系。方法采用双向MR方法,基于全基因组关联研究(genome-wide association studies,GWAS)数据库...目的通过应用孟德尔随机化(Mendelian randomization,MR)方法,系统探究10种尿毒症相关毒素及代谢物与CD8^(+)T细胞衰老表型之间的双向因果关系。方法采用双向MR方法,基于全基因组关联研究(genome-wide association studies,GWAS)数据库汇总数据,提取与10种尿毒症相关毒素及代谢物以及4种CD8^(+)T细胞衰老表型显著相关的单核苷酸多态性位点作为工具变量。逆方差加权法(inverse variance weighting,IVW)作为主要分析方法,同时采用MR-Egger、加权中位数法、简单众数法及加权众数法进行补充分析。通过Cochran’s Q检验、MR-Egger截距检验、MR-PRESSO及留一法等敏感性分析验证结果的稳健性与潜在多效性。结果MR分析显示,肉碱水平与终末分化CD8^(+)T细胞比例(IVW:β=1.71,95%CI:0.59~2.83,P=0.003)、CD45RA^(+)CD28^(-)CD8^(+)T细胞比例(IVW:β=2.23,95%CI:0.65~3.80,P=0.006)、CD28^(-)CD8^(+)T细胞比例(IVW:β=1.13,95%CI:0.11~2.15,P=0.030)正相关。犬尿氨酸水平与终末分化CD8^(+)T细胞比例正相关(IVW:β=1.69,95%CI:0.57~2.82,P=0.0003),而白介素-6水平与CD28^(-)CD8^(+)T细胞比例(IVW:β=0.28,95%CI:0.03~0.53,P=0.026)和CD45RA^(+)CD28^(-)CD8^(+)T细胞比例(IVW:β=0.41,95%CI:0.02~0.79,P=0.04)正相关。N^(2),N^(2)-二甲基鸟苷水平与CD45RA^(+)CD28^(-)CD8^(+)T细胞绝对计数(IVW:β=2.53,95%CI:0.51~4.55,P=0.014)正相关。反向MR分析显示,CD45RA^(+)CD28^(-)CD8^(+)T细胞绝对计数增加可降低肉碱水平(IVW:β=-0.00003,95%CI:-0.000062~-0.000004,P=0.024)。所有敏感性分析均支持主要结果的稳健性。结论部分尿毒症相关毒素及代谢物与CD8^(+)T细胞衰老之间存在双向因果关联,为尿毒症患者免疫功能紊乱的机制提供了新的因果证据与潜在干预靶点。展开更多
基金Supported by Grants from the"Yucai"Research Program of Changhai Hospital
文摘AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total T cells was detected by flow cytometry.Levels of total CD8+T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULTS:The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.
