布鲁菌病患者Th1、Th2和Th17细胞及其相关细胞因子的表达及意义

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目的:探讨辅助性T细胞Th1、Th2和Th17及其相关细胞因子在布鲁菌感染后急性期、慢性期及恢复期的免疫应答特点。方法:采用前瞻性研究,选择2017年1月至2018年12月于石河子大学医学院第一附属医院确诊的布鲁菌病患者130例为研究对象,包括急性期组(49例)、慢性期组(44例)、恢复期组(37例),并以同期健康体检者30例为对象纳入对照组,采集所有受试者外周血样本,流式细胞术检测外周血中Th1、Th2和Th17细胞的表达情况;流式液相多重蛋白定量技术(CBA)检测血清中细胞因子γ-干扰素(IFN-γ)、白细胞介素(IL)-4和IL-17A表达水平。结果:对照组和急性期、慢性期、恢复期组人群外周血Th1[(1.03 ± 0.85)%、(5.46 ± 3.54)%、(4.48 ± 2.26)%、(2.29 ± 2.25)%]、Th2[(4.72 ± 2.36)%、(7.00 ± 3.14)%、(13.99 ± 9.14)%、(5.89 ± 4.69)%]、Th17细胞表达比例[(2.09 ± 0.48)%、(3.04 ± 2.17)%、(3.61 ± 2.67)%、(2.74 ± 2.58)%]组间比较,差异均有统计学意义(n F = 20.95、21.15、2.90,n P均< 0.05);与对照组比较,急性期、慢性期组Th1、Th2、Th17细胞和恢复期组Th1细胞表达比例均较高(n P均< 0.05);与恢复期组比较,急性期、慢性期组Th1、Th2、Th17细胞表达比例均较高,但急性期组Th2细胞表达比例低于慢性期组(n P均< 0.05)。对照组和急性期、慢性期、恢复期组人群血清中IFN-γ、IL-4、IL-17A表达水平组间比较,差异均有统计学意义(n F = 7.79、15.85、7.55,n P均< 0.05);与对照组比较,急性期、慢性期组IFN-γ、IL-4、IL-17A和恢复期组IFN-γ、IL-4表达水平均较高(n P均< 0.05);与恢复期比较,急性期组IFN-γ、IL-4、IL-17A和慢性期组IFN-γ、IL-17A表达水平均较高(n P均< 0.05)。结束治疗时间< 12个月的恢复期患者Th1细胞表达比例显著高于结束治疗时间≥12个月的恢复期患者(n t = 2.26,n P < 0.05)。n 结论:患者感染布鲁菌后,急性期以Th1细胞免疫为主,慢性期以Th2细胞免疫为主,而Th17细胞免疫在急性期及慢性期的应答无明显差异。恢复期患者免疫功能在结束治疗时间< 12个月时可能依然存在异常,部分临床治愈的恢复期患者体内Th1细胞比例仍高相对较高,提示患者免疫功能尚未完全恢复。“,”Objective:To investigate the immune response characteristics of helper T cells Th1, Th2, Th17 and their related cytokines in acute, chronic and recovery phases after n Brucella infection.n Methods:Using prospective study, a total of 130 patients with brucellosis in the First Affiliated Hospital of Medical College of Shihezi University from January 2017 to December 2018 were selected as the research subjects, including acute phase group (49 cases), chronic phase group (44 cases), recovery phase group (37 cases), and 30 cases of healthy physical examination during the same period were included in the control group. The peripheral blood samples of all subjects were collected, and flow cytometry was used to detect Th1, Th2 and Th17 cells in the peripheral blood; the cytometry bead array (CBA) was used to detect the serum cytokines interferon-γ (IFN-γ), interleukin (IL)-4 and IL-17A expression levels.Results:In the control, acute phase, chronic phase and recovery phase groups, the differences of the expression ratios of Th1 [(1.03 ± 0.85)%, (5.46 ± 3.54)%, (4.48 ± 2.26)%, (2.29 ± 2.25)%], Th2 [(4.72 ± 2.36)%, (7.00 ± 3.14)%, (13.99 ± 9.14)%, (5.89 ± 4.69)%], and Th17 cells [(2.09 ± 0.48)%, (3.04 ± 2.17)%, (3.61 ± 2.67)%, (2.74 ± 2.58)%] were statistically significant (n F = 20.95, 21.15, 2.90, n P < 0.05). Compared with the control group, the expressions ratio of Th1, Th2, Th17 cells in acute and chronic phase groups and Th1 cells in recovery phase group were significantly higher ( n P < 0.05); compared with the recovery phase group, the expressions ratio of Th1, Th2 and Th17 cells in acute and chronic phase groups were significantly higher, but the expression ratio of Th2 cells in acute phase group was lower than that in chronic phase group ( n P < 0.05). The expression levels of IFN-γ, IL-4, and IL-17A in serum of control group, acute phase, chronic phase and recovery phase groups were significantly different ( n F = 7.79, 15.85, 7.55, n P < 0.05); compared with the control group, the expression levels of IFN-γ, IL-4, IL-17A in acute and chronic phase groups and IFN-γ, IL-4 in recovery phase group were significantly higher ( n P < 0.05); compared with the recovery phase group, the expression levels of IFN-γ, IL-4, IL-17A in acute phase group and IFN-γ, IL-17A in chronic phase group were significantly higher ( n P < 0.05). The expression ratio of Th1 cells in recovery phase patients who finished treatment for less than 12 months was significantly higher than that of recovery phase patients who finished treatment for ≥12 months ( n t = 2.26, n P < 0.05).n Conclusions:After patients are infected with n Brucella, Th1 cell immunity is dominant in acute phase, Th2 cell immunity is dominant in chronic phase, and there is no significant difference in the response of Th17 cell immunity between acute and chronic phases. The immune function of patients in the recovery phase may still be abnormal when the treatment time is less than 12 months. Some clinically cured patients in the recovery phase still have a relatively high proportion of Th1 cells, suggesting that the patient's immune function has not fully recovered.n
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