隐球菌性脑膜炎患者外周血中Th9和Th17细胞水平变化及意义

目的：比较初发隐球菌性脑膜炎患者治疗前后与健康对照人群外周血 CD4＋ T 细胞中 Th9和 Th17细胞的比值,探讨 Th9和 Th17细胞在隐球菌性脑膜炎发病机制中的作用。方法选取初发未经治疗隐球菌性脑膜炎患者及健康对照各12例,抽取隐球菌性脑膜炎患者治疗前和治疗后3周及健康对照的外周血,分离外周血单核细胞,应用流式细胞仪检测技术对3组病例外周血 CD4＋ T 细胞中 Th9和 Th17的比值进行比较。结果与健康对照相比,隐球菌性脑膜炎患者治疗前Th17表达下调,差异有统计学意义;在治疗好转患者中,治疗后 Th17表达显著上调,与治疗前及健康对照相比差异均有统计学意义。Th9在治疗前与健康对照相比无差异,在治疗后隐球菌性脑膜炎患者中表达上调。结论 Th17免疫途径是隐球菌性脑膜炎患者抵御隐球菌感染的重要免疫机制,隐球菌性脑膜炎发病及治疗拮抗可能与 Th17缺乏有关。     

Th17及Th1相关细胞因子与支气管哮喘的关系研究

目的:分析外周血Th17、Th1及相关细胞因子表达水平和支气管哮喘(bronchial asthma,BA)发生、发展的相关性研究。方法:回顾选取我院收治的BA病例57份,称作BA组,另选取呼吸系统正常的病例55例为对照组,检测两组入选者的外周血IL-2、TNF-α、Th17、IL-6、Th1指标表达差异,并进行多因素回归分析。结果:BA组Th17(0.62±1.67)%、Th1(1.45±0.48)%及Th1/Th17(2.33±1.28)均显著低于对照组(P均0.05);BA组TNF-α(27.46±8.12)pg/mL、IL-6(11.69±2.14)pg/mL表达量显著高于对照组,IL-2(2.58±3.89)pg/mL、IFN-γ(3.74±6.15)pg/mL含量均显著低于对照组(P均0.05);经Logistic回归分析,TNF-α、IL-6、IFN-γ、Th1/Th17、IL-2均和BA有密切相关性(P均0.05)。结论:IL-2、IFN-γ、Th1/Th17、TNF-α、IL-6表达水平均与BA有密切关联,可能是参与BA发病的主要原因,及早进行Th17、Th1及相关细胞因子检查有助于明确病情。     

沙门菌- 斑马鱼感染模型用于Th1/Th2 免疫应答的研究

目的:通过构建斑马鱼成鱼感染模型,研究鼠伤寒沙门菌感染对机体Th1/Th2免疫应答的影响。方法:用不同剂量细菌口饲感染8月龄的斑马鱼成鱼,绘制3周生存率曲线。观察各剂量下对成鱼的感染情况,并用实时荧光定量聚合酶链式反应检测肝脏Th1、Th2型细胞相关基因和细胞因子的mRNA转录水平,计算Th2/Th1相对表达量比值。结果:用105 CFU感染2周斑马鱼全部存活,第15天开始出现死亡,且在3周后死亡率达到50%;感染后3周解剖发现,肝脏、脾脏和肠道有明显红肿和糜烂;肝脏Th1、Th2型细胞相关基因和细胞因子mRNA转录水平明显向Th2偏移。结论:用105 CFU鼠伤寒沙门菌口饲感染斑马鱼成鱼构建的模型,能反映机体感染和免疫功能变化,可用于研究体内Th1/Th2免疫应答,为进一步研究鼠伤寒沙门菌感染与免疫机制提供了很好的实验工具。     

Deviated balance between Th1 and Th17 cells exacerbates acute graft-versus-host disease in mice

BackgroundTh1/Th17 imbalance had been indicated to mediate several kinds of inflammatory diseases. We deduce that Th1/Th17 imbalance might also contribute to the pathogenesis of acute graft-versus-host disease (GVHD). This study is to investigate the relation between Th1/Th17 imbalance and acute GVHD.MethodsWe applied a murine GVHD model of C57BL/6 (H-2^b) donor to BALB/c (H-2^d) recipient by treating the recipients with low dose of halofuginone (HF), which is competent in selectively inhibiting Th17 differentiation and facilitating Th1 differentiation. Recipient mice were monitored for survival rate, body weight change, clinical symptoms and pathological evidence of acute GVHD. We also measured the proportions of Th1 and Th17 cells in circulation and expression levels of IFN-γ and IL-17A in tissues involved in GVHD.ResultsFirstly, we confirm the existence of Th1/Th17 imbalance in acute GVHD and Th1/Th17 imbalance positively correlates with severity of acute GVHD. Secondly, low dose of HF augments Th1/Th17 imbalance by driving the Th1/Th17 balance to a Th1-dominant reaction. Finally, augmented Th1/Th17 imbalance leads to aggravated systemic GVHD. An increased Th1-type reaction results in aggravated hepatic and intestinal GVHD, and inhibiting Th17 differentiation is sufficient to alleviate pulmonic impairment.ConclusionOur study is indicative for a critical role of Th1/Th17 imbalance in the pathogenesis of murine GVHD.     

The attenuation of Th1 and Th17 responses via autophagy protects against methicillin-resistant Staphylococcus aureus-induced sepsis

Whether autophagy affects methicillin-resistant Staphylococcus aureus (MRSA)-induced sepsis and the associated mechanisms are largely unknown. This study investigated the role of autophagy in MRSA-induced sepsis. The levels of microtubule-associated protein light chain 3 (LC3)-II/I, Beclin-1 and p62 after USA300 infection were examined by Western blotting and immunohistochemical staining. Bacterial burden analysis, hematoxylin-eosin staining, and Kaplan–Meier analysis were performed to evaluate the effect of autophagy on MRSA-induced sepsis. IFN-γ and IL-17 were analyzed by ELISA, and CD4⁺ T cell differentiation was assessed by flow cytometry. Our results showed that LC3-II/I and Beclin-1 were increased, while p62 was decreased after infection. Survival rates were decreased in the LC3B^−/− and Beclin-1^+/− groups, accompanied by worsened organ injuries and increased IFN-γ and IL-17 levels, whereas rapamycin alleviated organ damage, decreased IFN-γ and IL-17 levels, and improved the survival rate. However, there was no significant difference in bacterial burden. Flow cytometric analysis showed that rapamycin treatment decreased the frequencies of Th1 and Th17 cells, whereas these cells were upregulated in the LC3B^−/− and Beclin-1^+/− groups. Therefore, autophagy plays a protective role in MRSA-induced sepsis, which may be partly associated with the alleviation of organ injuries via the downregulation of Th1 and Th17 responses. These results provide a nonantibiotic treatment strategy for sepsis.     

In vitro Th1 cytokine-independent Th2 suppressive effects of bifidobacteria

A comparison between 17 strains of lactic acid bacteria and 15 strains of bifidobacteria indicated that bifidobacteria induced significantly lower levels of interleukin-12 (IL-12) in murine splenic cells. The present study aims to evaluate the effect and mechanism of Bifidobacterium longum BB536, a probiotic strain, in suppressing antigen-induced Th2 immune response in vitro. BB536 suppressed immunoglobulin (Ig) E and IL-4 production by ovalbumin-sensitized splenic cells, but induction of Th1-inducing cytokine production, such as IL-12 and gamma interferon (IFN-gamma) tended to be lower compared with lactic acid bacteria. Neutralization with antibodies to IL-12, IFN-gamma, IL-10 and transforming growth factor beta indicated negative involvement of Th1-inducing cytokines and regulatory cytokines in the suppression of Th2 immune response by BB536, especially when treated at higher doses of BB536 (>10 microg cells/ml). Furthermore, BB536 induced the maturation of immature bone marrow-derived dendritic cells (BM-DCs), and suppressed antigen-induced IL-4 production mediated by BM-DCs. These results suggested that BB536 suppressed Th2 immune responses, partially independent of Th1-inducing cytokines and independent of regulatory cytokines, mediated by antigen-presenting cells such as dendritic cells.     

先兆流产患者阴道微生态与Th1及Th2细胞因子的关系探讨

目的探讨先兆流产患者阴道微生态与Th1及Th2类细胞因子的关系。方法回顾性分析2019年2月-2020年2月医院收治的98例先兆流产患者的资料,记为A组,另回顾性分析同期在该院体检的92例健康孕妇的资料,记为B组。对比A组和B组阴道微生物菌群组成,对比A组和B组血清Th1及Th2类细胞因子水平,采用Pearson相关性分析,分析先兆流产患者阴道微生物菌群相对丰度与血清Th1及Th2类细胞因子水平的相关性。结果A组阴道微生物群Chao1指数、Shannon指数均低于B组(P<0.05),A组阴道微生物群门水平上放线菌门、变形菌门、拟杆菌门和属水平加德纳菌、奇异菌属、普氏菌属相对丰度均高于B组(P<0.05),门水平厚壁菌门、梭杆菌门和属水平乳酸杆菌属的相对丰度均低于B组(P<0.05);A组Th1类细胞因子TNFα和IL2水平高于B组(P<0.05),Th2类细胞因子IL4和IL10水平低于B组(P<0.05);采用Pearson相关性检验,先兆流产患者阴道微生物群门水平厚壁菌门、梭杆菌门、属水平乳酸杆菌属的相对丰度分别与TNFα和IL2水平呈负相关(P<0.05),分别与IL4和IL10水平呈正相关(P<0.05),放线菌门、变形菌门、拟杆菌门、加德纳菌属、奇异菌属、普氏菌属的相对丰度分别与TNFα和IL2水平呈正相关(P<0.05),分别与IL4和IL10水平呈负相关(P<0.05)。结论先兆流产患者阴道微生物菌群分布与血清Th1及Th2细胞因子水平相关。     

Th1型和Th2型细胞因子在口腔扁平苔藓患者外周血中的表达及临床意义

目的:研究口腔扁平苔藓(OLP1)患者Th1型和Th2型细胞因子的表达及临床意义。方法:选取2013年1月至2014年3月于我院就诊的21例充血糜烂型及14例光滑型OLP患者为研究对象,18例正常人为对照组,采用密度梯度离心法对各组外周血单个核细胞进行分离,酶联免疫吸附剂测定(ELISA)法对各组外周血单个核细胞中的IL-4和IFN-gamma的表达进行检测,逆转录-聚合酶链反应法对各组血清中IL-4 m RNA和IFN-gamma m RNA的表达进行检测。结果:与正常对照组相比,OLP患者IL-4m RNA及蛋白的表达均增高,而IFN-gamma m RNA及蛋白的表达则降低,差异均有显著统计学意义(均P0.01)。充血糜烂型及光滑型OLP患者组间比较发现,IL-4 m RNA和IFN-gamma m RNA及蛋白的表达差异无统计学意义(P0.05)。结论:OLP发病机制与Th1与Th2的表达失衡有关,为临床治疗提供参考。     

Th1/Th2平衡调节与疾病发生的研究进展

正常情况下,辅助性T淋巴细胞亚群Th1/Th2细胞处于平衡状态,Th1/Th2平衡失调并向Th1或Th2状态转化的趋势称为Th1/Th2的漂移。习惯上把Th1及其细胞因子占优势的状态称为Th1状态,Th2及其细胞因子占优势的状态称为Th2状态。Th1/Th2平衡影响细胞因子网络的平衡,与许多疾病的发生、发展、治疗、转归有密切的关系。现就Th1/Th2平衡与人类相关疾病间的关系及相关研究作一综述。     

轮状病毒致乳鼠肠道外感染Th1/Th2细胞因子变化的研究

目的通过复制轮状病毒（RV）肠道外感染乳鼠的动物模型,检测接种后乳鼠体内Th1/Th2平衡改变,对RV肠道外感染后机体免疫状态进行初步研究。方法48只乳鼠随机均分为3组：肠道外组、肠道内组和正常对照组。肠道外组通过腹腔注射猴RVSA11株,肠道内组灌胃等量RV悬液,对照组无特殊处理。分别在接种后第4天、第8天处死乳鼠,收集标本,观察心、肝、肾、肺等脏器病理变化,用ELISA法检测血清中IL-10和IFN-γ的表达。结果光镜下肠道外组乳鼠肾、肝、肺和脾脏出现病理改变。感染后第4天,肠道内、外组乳鼠血清IFN-γ水平均高于正常组,到第8天明显下降,基本达到基线水平;IL-10在肠道外组第4天增高,到第8天小幅下降,但仍然高于正常组;而肠道内组IL-10无明显改变。结论RV肠道外感染早期呈现Th1-Th2混合反应,而后期则以IL-10的表达为主,T细胞向Th2型免疫应答方向偏离,Th1/Th2细胞因子失衡机制可能是RV肠道外感染的重要因素。     

菌群失调小鼠感染鼠伤寒沙门菌后Th1和Th2细胞因子的动态研究

目的研究鼠伤寒沙门菌感染小鼠在菌群失调下Th细胞因子的动态变化,以探讨菌群失调对沙门菌感染的免疫机制。方法分别建立菌群失调、感染和空白对照的小鼠模型。各组动物在感染不同时点处死,观察小肠、肝脏和脾脏病理改变。采用流式细胞仪检测脾脏细胞中IFN-γ和IL-4表达,以此代表Th1和Th2细胞。结果菌群失调组病理损害最重,Th1明显增加,表达水平高,Th2变化不大,Th1/Th2比值升高。结论菌群失调后,能够加重小鼠感染鼠伤寒沙门菌引起的的Th1型反应,产生炎症性损伤。     

Th1、Th2和Th17型细胞在类风湿性关节炎和系统性红斑狼疮中的活化特点

探讨Th1、Th2和Th17型细胞在类风湿性关节炎(RA)和系统性红斑狼疮(SLE)发病机制中的作用。收集37例RA患者、25例SLE患者和34例健康人的抗凝血,应用ELISA检测血清中IFN-γ、IL-10和IL-17的水平。与健康对照组比较,RA和SLE患者血清中IFN-γ的水平均具有统计学意义(P<0.05);SLE患者IL-10水平出现有意义的升高(P<0.05);而RA患者IL-17的升高具有统计学意义(P<0.05)。由此提示Th1、Th2和Th17细胞在自身免疫性疾病中均发挥不同的重要作用。     

支气管哮喘患儿肺功能状态及Th1Th2指标的变化观察

目的:观察支气管哮喘患儿肺功能状态及Th1Th2指标的变化情况。方法:选取2013年10月~2015年8月本院诊治的65例支气管哮喘患儿为观察组,另选择同期接受体检的健康同龄儿童65名为对照组。比较两组患儿肺功能状态及Th1Th2指标,观察不同严重程度及分期支气管哮喘患儿的肺功能状态及Th1Th2指标。结果:观察组患儿肺功能指标及血清Th1Th2指标均低于对照组,差异具有统计学意义(P0.05);观察组患儿发作期肺功能指标及血清Th1Th2指标明显低于缓解期,差异具有统计学意义(P0.05);重度患儿肺功能指标及血清Th1Th2指标均低于轻度及中度患儿,差异具有统计学意义(P0.05);中度患儿肺功能指标及血清Th1Th2指标低于轻度患儿,差异具有统计学意义(P0.05)。结论:支气管哮喘患儿肺功能状态及Th1Th2指标的变化较大,且疾病分期与疾病严重程度对其检测结果也有较大影响。     

T-helper (Th)1/Th2 imbalance in the peripheral blood of dogs with malignant tumor

T helper type 1 cell (Th1)/Th2 imbalance has been observed in a variety of pathological conditions, including malignant diseases. We evaluated the Th1/Th2 in peripheral blood Th cells by means of intracytoplasmic cytokine analysis in 11 dogs with advanced malignant tumor; four of them showed metastatic tumor. The percentage of Th1 was significantly lower and the percentage of Th2 was significantly higher in diseased dogs compared to healthy dogs. The percentage of Th1 in three patients with metastatic tumor was significantly lower than that in the patients with non-metastatic tumor. We conclude that the Th1/Th2 balance was polarized to Th2 in dogs with cancer.     

特应性皮炎患儿外周血miR-122a和miR-146a水平与Th1/Th2/Th17免疫平衡的相关性分析

摘要 目的：探讨特应性皮炎（AD）患儿外周血微小核糖核酸（miRNA）-122a和miR-146a水平与辅助性T细胞（Th）1/Th2/Th17免疫平衡的相关性。方法：选取2020年5月～2023年5月石家庄市妇幼保健院皮肤科收治的AD患儿100例为AD组,根据特应性皮炎评分（SCORAD）分为轻度组31例、中度组41例、重度组28例,另选取同期100名体检健康儿童为对照组。采用实时荧光定量聚合酶链式反应检测外周血miR-122a、miR-146a水平,流式细胞术检测外周血Th1、Th2、Th17细胞比例,酶联免疫吸附法检测外周血Th1、Th2、Th17相关细胞因子[白细胞介素（IL）-2、干扰素-γ（IFN-γ）、IL-4、IL-13、IL-17、IL-22]水平,并计算Th1/Th2/Th17比值。采用Pearson/Spearman相关性分析AD患儿外周血miR-122a、miR-146a与Th1、Th2、Th17和相关细胞因子及Th1/Th2/Th17的相关性。结果：AD组外周血miR-122a、miR-146a、Th1、Th1/Th2/Th17、IL-2、IFN-γ水平低于对照组,Th2、Th17、IL-4、IL-13、IL-17、IL-22水平高于对照组（P均＜0.05）。轻度组、中度组、重度组外周血miR-122a、miR-146a、Th1、Th1/Th2/Th17、IL-2、IFN-γ水平依次降低,Th2、Th17、IL-4、IL-13、IL-17、IL-22水平依次升高（P均＜0.05）。Pearson/Spearman相关性分析显示,AD患儿外周血miR-122a、miR-146a与Th1、Th1/Th2/Th17、IL-2、IFN-γ水平呈正相关（r/rs分别为0.679、0.677、0.684、0.706、0.693、0.689、0.671、0.694,P均＜0.001）,与Th2、Th17、IL-4、IL-13、IL-17、IL-22呈负相关（r/rs分别为-0.690、-0.680、-0.681、-0.669、-0.675、-0.676、-0.676、-0.686、-0.682、-0.674、-0.680、-0.689,P均＜0.001）。结论：AD患儿外周血miR-122a、miR-146a水平降低,与病情严重程度密切相关,可能通过调节Th1/Th2/Th17免疫平衡参与AD发生发展。     

Th1/Th2类细胞因子的变化对急性免疫性肝损伤的影响研究

目的探讨Th1/Th2类细胞因子的变化对ConA诱导的急性免疫性肝损伤的机制,以及脾脏对急性免疫性肝损伤的影响作用。方法将Balb/c小鼠随机分为两组：正常对照组,肝损伤组。正常对照组尾静脉注射等量生理盐水,肝损伤组尾静脉注射12.5mg/Kg ConA一次。各组分别于ConA注射后8h,24h,72h取材,进行下列研究：①HE染色观察各组小鼠肝脏病理学改变。②经眼球取血,收集血清测ALT和AST。③收集各组小鼠血清及新鲜肝、脾组织（各100mg）,获取肝、脾组织裂解液。用多参数细胞因子检测技术即FlowCytomix技术,通过流氏细胞仪对荧光素PE信号强度的检测,实现对各组小鼠血清、肝组织、脾组织内多种Th1/Th2类因子的定性定量分析。结果①HE染色：正常对照组肝组织结构正常。肝损伤组8h时表现为急性肝损伤表现,24h时可见大片坏死灶,72h时肝损伤缓解。②血清ALT和AST检测：正常对照组3个时间点内无明显升高,肝损伤组3个时间段内ALT和AST均高于正常对照组,有显著性差异。③Th1/Th2细胞因子检测结果：肝脏：肝损伤组8h时Th1和Th2类细胞因子均明显升高,与正常对照组比较有显著性差异,24h后开始下降,降至正常水平或正常水平以下,呈明显下降趋势。血清：肝损伤组Th1,Th2类细胞因子8h均升高,24h后逐步降低。脾脏：肝损伤组Th1,Th2类细胞因子8h时均升高,与正常对照组比较,有显著性差异,24h时明显降低。结论①ConA诱导的急性免疫性肝损伤主要是由Th1类细胞、巨噬细胞和Th2类细胞分泌的炎性因子所造成。②脾脏通过Th1/Th2类细胞因子的分泌对急性免疫性肝损伤起到免疫调控作用。     

A novel chronic stress-induced shift in the Th1 to Th2 response promotes colon cancer growth

Epidemiological data have shown that stress and other psychological factors might influence cancer onset and progression. However, to date, the mechanisms are not well understood. In the present study, we used chronic exposure to a scream as a novel form of sound stress to explore the influence of the chronic stress burden on colon cancer progression, and changes in the immune system were observed. Chronic exposure to scream sound stress induced freezing behavior in the mice and decreased the bodyweight gain. It also caused changes in the adrenal gland and increased serum corticosterone and norepinephrine levels. Cytokine microarray analysis showed changes in the levels of Th1 and Th2 cytokines. The chronic scream sound stress caused a shift from the Th1 to the Th2 response both in the circulation and in tumor-infiltrated lymphocytes, and it promoted colon cancer progression significantly. Taken together, chronic scream sound stress can be conveniently used as a novel chronic stress model. Chronic stress contributes to colon cancer progression and induces a Th1/Th2 imbalance in the mouse immune system, which is considered critical during cancer progression.