中华皮肤科杂志 ›› 2016, Vol. 49 ›› Issue (8): 551-554.

• 论著 • 上一篇    下一篇

程序性死亡分子1及其配体1在尖锐湿疣患者外周血T淋巴细胞的表达及意义

陈惠勇1,杨文林1,林立1,黄新宇1,尹嘉文2,陈嘉惠2   

  1. 1. 广州医科大学附属第二医院皮肤科
    2. 广州医科大学附属第二医院
  • 收稿日期:2016-02-14 修回日期:2016-04-08 发布日期:2016-08-05
  • 通讯作者: 杨文林 E-mail:yangwenlin@21cn.com

Programmed death?1 and programmed death ligand?1 s on peripheral blood T lymphocytes from patients with condyloma acuminatum and their significance

  • Received:2016-02-14 Revised:2016-04-08 Published:2016-08-05

摘要:

目的 研究程序性死亡分子1(PD?1)及其配体1(PD?L1)在尖锐湿疣患者外周血T淋巴细胞表面的表达,探讨PD?1/PD?L1信号通路在尖锐湿疣患者细胞免疫中的作用。方法 采用流式细胞仪检测30例尖锐湿疣患者和20例健康对照者外周血CD4+、CD8+ T淋巴细胞表面PD?1、PD?L1的表达及CD4+、CD8+ T淋巴细胞计数,采用双抗体夹心酶联免疫吸附测定法检测血清中白细胞介素2(IL?2),干扰素γ(IFN?γ)的水平,比较两组间的差异,分析尖锐湿疣患者外周血T淋巴细胞表面PD?1、PD?L1表达水平与CD4+、CD8+ T淋巴细胞计数、细胞因子IL?2、IFN?γ的相关性。结果 尖锐湿疣组CD4+、CD8+ T淋巴细胞PD?1表达水平(分别为9.48% ± 3.31%和12.52% ± 3.17%)、PD?L1表达水平(4.40% ± 1.46%、7.07% ± 2.23%)分别高于健康对照组(PD?1:7.12% ± 2.16%、9.95% ± 2.17%,t = 2.81、3.16,均P < 0.01;PD?L1:3.26% ± 1.13%、5.39% ± 1.69%,t = 2.96、2.88,均P < 0.01)。尖锐湿疣组CD4+ T淋巴细胞计数(727.43 ± 138.59个/μl)低于对照组(804.25 ± 92.83个/μl,t = 2.17,P < 0.05),CD8+ T淋巴细胞计数与对照组差异无统计学意义(t = 1.24,P > 0.05),CD4+/CD8+比值(1.23 ± 0.35)低于对照组(1.46 ± 0.34,t = 2.24,P < 0.05)。尖锐湿疣组血清IL?2、IFN?γ水平均低于对照组(t = 2.12、2.16,均P < 0.05)。相关分析显示,尖锐湿疣患者外周血CD4+ T淋巴细胞表面PD?1、PD?L1表达水平分别与CD4+ T淋巴细胞计数、CD4+/CD8+比值、IL?2、IFN?γ水平均呈负相关(P < 0.05);CD8+ T淋巴细胞表面PD?1、PD?L1表达水平与CD4+/CD8+比值均呈负相关(P < 0.05),与CD8+ T淋巴细胞计数无相关性(P > 0.05)。结论 尖锐湿疣患者外周血T淋巴细胞高表达的PD?1可能通过与其配体PD?L1作用形成PD?1/PD?L1信号通路,抑制T淋巴细胞免疫应答,导致尖锐湿疣患者CD4+ T淋巴细胞数量减少,CD4+/CD8+比值下降,IL?2、IFN?γ减少。

Abstract:

Chen Huiyong, Yang Wenlin, Lin Li, Huang Xinyu, Yin Jiawen, Chen Jiahui Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China Corresponding author: Yang WL, Email: yangwenlin@21cn.com 【Abstract】 Objective To measure the s of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) on peripheral blood T lymphocytes of patients with condyloma acuminatum (CA), and to investigate their role in cellular immunity in these patients. Methods Peripheral blood samples were obtained from 30 patients with CA(CA group)and 20 healthy human controls (control group). Flow cytometry was conducted to detect the s of PD-1 and PD-L1 on the surfaces of peripheral blood CD4+ and CD8+ T lymphocytes, and to determine the counts of CD4+ and CD8+ T lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of serum interleukin-2 (IL-2) and interferon-γ (IFN-γ). Statistical analyses were carried out to compare the above parameters between the two groups, and to assess the relationship of PD-1 and PD-L1 s with the counts of CD4+ and CD8+ T lymphocytes as well as with the serum levels of IL-2 and IFN-γ. Results There was a significant increase in the rates of PD-1 and PD-L1 on CD4+ T lymphocytes (PD-1: 9.48% ± 3.31% vs. 7.12% ± 2.16%, t = 2.81, P < 0.01; PD-L1: 4.40% ± 1.46% vs. 3.26% ± 1.13%, t = 3.16, P < 0.01) and CD8+ T lymphocytes (PD-1:12.52% ± 3.17% vs. 9.95% ± 2.17%, t = 3.16, P < 0.01; PD-L1: 7.07% ± 2.23% vs. 5.39% ± 1.69%, t = 2.88, P < 0.01) in the CA group compared with the control group. Moreover, the CA group showed significantly lower counts of CD4+ T lymphocytes (727.43 ± 138.59/μl vs. 804.25 ± 92.83/μl, t = 2.17, P < 0.05) and CD4/CD8 ratio (1.23±0.35 vs. 1.46±0.34, t = 2.24, P < 0.05) than the control group, while no significant difference was observed in CD8+ T lymphocyte counts between the CA group and control group (613.60±121.60/μl vs. 572.45±103.08/μl, t = 1.24, P > 0.05). The levels of serum IL-2 and IFN-γ were both lower in the CA group than in the control group(t = 2.12, 2.16, respectively, both P < 0.05). In the CA group, PD-1 and PD-L1 levels on peripheral blood CD4+ T lymphocytes were both negatively correlated with CD4+ T lymphocyte counts, the CD4/CD8 ratio, as well as IL-2 and IFN-γ serum levels(all P < 0.05), and those on peripheral blood CD8+ T lymphocytes were also negatively correlated with the CD4/CD8 ratio(all P < 0.05), but uncorrelated with CD8+ T lymphocyte counts(both P > 0.05). Conclusion PD-1 was highly expressed on peripheral blood T lymphocytes from patients with CA, which may inhibit T lymphocyte-mediated immune response, decrease CD4+ T lymphocyte counts, the CD4/CD8 ratio as well as IL-2 and IFN-γ serum levels by interacting with its ligand PD-L1 and forming the PD-1/PD-L1 signaling pathway.

引用本文

陈惠勇 杨文林 林立 黄新宇 尹嘉文 陈嘉惠. 程序性死亡分子1及其配体1在尖锐湿疣患者外周血T淋巴细胞的表达及意义[J]. 中华皮肤科杂志, 2016,49(8):551-554. doi: