Th17和调节性T细胞在人类免疫缺陷病毒疾病进展中的作用及其调控机制

Role and regulatory mechanisms of Th17 and regulatory T cells in the progression of HIV infection

摘要:

目的 本研究通过观察人类免疫缺陷病毒（HIV）感染者外周血Th17、Treg细胞及其相关转录因子、细胞因子的表达，进一步揭示Th17、Treg细胞的调控机制及其在HIV感染者疾病进展中的作用。方法 选取2019年1月—2019年10月河南省上蔡县HIV感染者80例作为研究组，选取同地区健康人群20例作为对照组。采用流式细胞术检测外周血CD4⁺T、CD8⁺T及外周血单个核细胞Th17、Treg，酶联免疫吸附试验检测血浆中细胞因子白细胞介素-17（IL-17）、IL-23水平，实时聚合酶链反应检测转录因子ROR-γt及Foxp3 mRNA表达，Pearson法分析Th17、Treg与CD4⁺T的相关性。结果 研究组CD4⁺T、CD4⁺T/CD3⁺T、CD4⁺T/CD8⁺T低于对照组（P <0.05），CD8⁺T和CD8⁺T/CD3⁺T高于对照组（P <0.05）。研究组Th17/CD4⁺T、Th17/Treg低于对照组（P <0.05），Treg/CD4⁺T高于对照组（P <0.05）。研究组ROR-γt mRNA高于对照组（P <0.05），Foxp3 mRNA低于对照组（P <0.05）。研究组IL-17、IL-23水平低于对照组（P <0.05）。Pearson相关性分析结果表示，Th17细胞百分比与CD4⁺T细胞计数呈正相关（r =0.293，P <0.05），Treg细胞百分比与CD4⁺T细胞计数呈负相关（r =-0.198，P <0.05）。结论 HIV感染能降低Th17细胞、升高Treg细胞，破坏机体免疫平衡，其机制与调控转录因子ROR-γt、Foxp3及细胞因子IL-17、IL-23表达有关，Th17细胞、Treg细胞与HIV感染者疾病进展密切相关。

Abstract:

Objective To observe the levels of Th17 and Treg cells along with their associated transcription factors and cytokines in peripheral blood of HIV-infected individuals, and to further reveal the regulatory mechanisms of Th17 and Treg cells and their roles in the progression of HIV infection.Methods From January 2019 to October 2019, the 80 HIV-infected individuals from a region in Henan Province were selected as the study group, and 20 healthy people from the same area were included as the control group. The levels of CD4⁺ and CD8⁺ T cells in peripheral blood and Th17 and Treg cells within peripheral blood mononuclear cells were detected by flow cytometry. The plasma levels of interleukin (IL)-17 and IL-23 were detected by enzyme linked immunosorbent assay. The mRNA expressions of transcription factors ROR-γt and Foxp3 were detected by quantitative real-time polymerase chain reaction. Pearson or Spearman method was used to analyze the correlations between levels of Th17 and Treg cells and the count of CD4⁺ T cells.Results The absolute count of CD4⁺ T cells and ratios of CD4⁺/CD3⁺ T cells and CD4⁺/CD8⁺ T cells in the study group were lower than those in the control group (P < 0.05), while the absolute count of CD8⁺ T cells and the ratio of CD8⁺/CD3⁺ T cells in the study group were higher than those in the control group (P < 0.05). The ratios of Th17/CD4⁺ T cells and Th17/Treg cells in the study group were lower than those in the control group (P < 0.05), whereas the ratio of Treg/ CD4⁺ T cells in the study group was higher than that in the control group (P < 0.05). Compared with the control group, the mRNA expression of ROR-γt was higher (P < 0.05), and that of Foxp3 was lower in the study group (P < 0.05). The levels of IL-17 and IL-23 in the study group were lower than those in the control group (P < 0.05). Pearson correlation analysis revealed that the percentage of Th17 cells was positively correlated with the count of CD4⁺ T cells (r = 0.293, P < 0.05), and that the percentage of Treg cells was negatively correlated with the count of CD4⁺ T cells (r = -0.198, P < 0.05).Conclusions HIV infection reduces the level of Th17 cells while increasing the level of Treg cells, disrupting the immune balance in the body. The mechanism is related to the regulation of the expressions of transcription factors ROR-γt and Foxp3 and cytokines IL-17 and IL-23. Th17 and Treg cells are closely associated with the disease progression of HIV-infected individuals.