载脂蛋白E(apolipoprotein E, APOE)是一种多功能蛋白,肝细胞、星形胶质细胞、巨噬细胞等多种体细胞均可以合成APOE。APOE除参与脂代谢外,还具有免疫调节作用,并被证明在乙型肝炎病毒(hepatitis B virus, HBV)、丙型肝炎病毒(hepatitis ...载脂蛋白E(apolipoprotein E, APOE)是一种多功能蛋白,肝细胞、星形胶质细胞、巨噬细胞等多种体细胞均可以合成APOE。APOE除参与脂代谢外,还具有免疫调节作用,并被证明在乙型肝炎病毒(hepatitis B virus, HBV)、丙型肝炎病毒(hepatitis C virus, HCV)和人类免疫缺陷病毒(human immunodeficiency virus, HIV)等多种病毒感染中发挥重要作用。最近研究显示,APOE基因多态性(gene polymorphism)与严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-COV-2)的易感性及感染后的严重程度和病死率相关。为了更全面地认识APOE的功能,现就APOE的免疫调节功能及在不同病毒感染过程中的作用作一概述。展开更多
Background Regulatory T cells （Tregs） may play an important role in immunopathology during HIV-1 infection. Transcription factor forkhead box P3 （FoxP3） orchestrates the development of Tregs and is a useful marker...Background Regulatory T cells （Tregs） may play an important role in immunopathology during HIV-1 infection. Transcription factor forkhead box P3 （FoxP3） orchestrates the development of Tregs and is a useful marker to identify this population. Using a FoxP3 phenotype to define Tregs, we investigated the level and phenotype of peripheral blood natural CD4~Tregs and assessed the relationship between the frequencies and absolute numbers of CD4＋Tregs and disease progression among untreated HIV-infected men who have sex with men （HIV^MSM） in China. Methods Fifty-two untreated HIV^＋MSM with CD4^＋T-cell counts of 〈350 cells/μl or 〉350 cells/μl were compared in a cross- sectional study. Twelve age-matched HIV-uninfected MSM and nine patients receiving antiretroviral therapy for at least 1 year were also included. Expression of CD25, CD127, CD45RA, CCR7 and CTLA-4 was assessed on CD4^＋Tregs using polychromatic flow cytometry. Results The percentage of CD4^＋Tregs was increased significantly, whereas CD4^＋Tregs expressed less CTLA-4 in HIV＊MSM compared with controls. CD4^＋Tregs displayed predominantly an effector memory phenotype （CD45RA-CCR7-）, phenotypically distinct from conventional CD4^＋T cells. Moreover, the expansive frequencies of CD4^＋Tregs coincided with lower CD4＋T-cell counts and higher viral loads whereas the absolute numbers of CD4^＋Tregs were associated with higher CD4^＋T-cell counts and lower viral loads. The expansion of Tregs was also associated with CD8^＋T-cell activation. Conclusion Increased proportions and decreased numbers of CD4^＋Tregs are associated with HIV progression, and their functions may impair with the progression of HIV infection.展开更多
基金This study was supported by grants from the National Natural Science Foundation （No. 30872354 and No. U1204811）, the Youth Innovation Fund of the First Affiliated Hospital of Zhengzhou University, and National Grand Program on Key Infectious Disease Control and Prevention （No. 2008ZX 10001-015） of China.
文摘Background Regulatory T cells （Tregs） may play an important role in immunopathology during HIV-1 infection. Transcription factor forkhead box P3 （FoxP3） orchestrates the development of Tregs and is a useful marker to identify this population. Using a FoxP3 phenotype to define Tregs, we investigated the level and phenotype of peripheral blood natural CD4~Tregs and assessed the relationship between the frequencies and absolute numbers of CD4＋Tregs and disease progression among untreated HIV-infected men who have sex with men （HIV^MSM） in China. Methods Fifty-two untreated HIV^＋MSM with CD4^＋T-cell counts of 〈350 cells/μl or 〉350 cells/μl were compared in a cross- sectional study. Twelve age-matched HIV-uninfected MSM and nine patients receiving antiretroviral therapy for at least 1 year were also included. Expression of CD25, CD127, CD45RA, CCR7 and CTLA-4 was assessed on CD4^＋Tregs using polychromatic flow cytometry. Results The percentage of CD4^＋Tregs was increased significantly, whereas CD4^＋Tregs expressed less CTLA-4 in HIV＊MSM compared with controls. CD4^＋Tregs displayed predominantly an effector memory phenotype （CD45RA-CCR7-）, phenotypically distinct from conventional CD4^＋T cells. Moreover, the expansive frequencies of CD4^＋Tregs coincided with lower CD4＋T-cell counts and higher viral loads whereas the absolute numbers of CD4^＋Tregs were associated with higher CD4^＋T-cell counts and lower viral loads. The expansion of Tregs was also associated with CD8^＋T-cell activation. Conclusion Increased proportions and decreased numbers of CD4^＋Tregs are associated with HIV progression, and their functions may impair with the progression of HIV infection.
