Th22细胞与支气管哮喘

支气管哮喘是一种临床上常见的呼吸道疾病,研究发现CD4＋T细胞在哮喘的发病过程中起重要作用。Th22细胞是最近发现的一类CD4＋T细胞功能亚群之一,其主要效应因子IL-22在炎症性疾病、组织修复、创口愈合及自身免疫性疾病中起重要作用,但其具体机制尚未完全清楚。从Th22的细胞因子来源、生物学特性、分化和调控出发,简要探讨Th22细胞与哮喘之间的可能关系。     

炎症性肠病患者Th22细胞亚群和IL-22水平变化及其临床意义

目的探讨Th22细胞亚群和血清白介素-22(IL-22)水平在炎症性肠病(IBD)患者中的变化及其临床意义。方法选取2016年1月至2018年4月我院收治的125例IBD患者作为研究对象,其中克罗恩病(CD)组患者65例,溃疡性结肠炎(UC)组患者60例。选取同期进行体检的健康者50例作为对照组。比较各组对象Th22细胞亚群,血清IL-22、C-反应蛋白(CRP)、红细胞沉降率(ESR)水平,并进行相关性分析。结果 CD组和UC组患者Th22细胞比例及IL-22、CRP、ESR水平均显著高于对照组(均P0.05),CD组患者Th22细胞比例及IL-22、CRP、ESR水平均显著高于UC组(均P0.05)。CD组和UC组患者随着病情活动性的增强其Th22细胞比例及IL-22、CRP、ESR水平不断上升(均P0.05)。Pearson相关性分析显示,IBD患者Th22细胞亚群、IL-22水平与疾病活动度及CRP、ESR水平均呈正相关(均P0.05)。结论 Th22细胞亚群和IL-22水平与IBD患者病情严重程度关系密切,提示Th22细胞亚群和IL-22可能参与IBD发病过程中的炎症过程。     

A High Frequency of Circulating Th22 and Th17 Cells in Patients with New Onset Graves’ Disease

T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of autoimmune diseases. However, their roles in the pathogenesis of Graves’disease (GD) are unclear. This study is aimed at examining the frequency of peripheral blood Th22, Th17, and Th1 cells and the levels of plasma IL-22, IL-17, and IFN-γ in patients with GD. A total of 27 patients with new onset GD and 27 gender- and age-matched healthy controls (HC) were examined for the frequency of peripheral blood Th22, Th17, and IFN-γ cells by flow cytometry. The concentrations of plasma IL-22, IL-17, and IFN-γ were examined by enzyme-linked immunosorbent assay. The levels of serum TSHR antibodies (A-TSHR), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were examined by radioimmunoassay and chemiluminescent assay, respectively. The levels of serum TSAb were examined by enzyme-linked immunosorbent assay. In comparison with those in the HC, significantly elevated percentages of Th22 and Th17 cells, but not Th1 cells, and increased levels of plasma IL-22 and IL-17, but not IFN-γ, were detected in GD patients (P<0.0001, for both). The percentages of both Th22 and Th17 cells and the levels of plasma IL-22 and IL-17 were correlated positively with the levels of serum TSAb in GD patients (r = 0.7944, P<0.0001; r = 0.8110, P<0.0001; r = 0.7101, p<0.0001; r = 0.7407, p<0.0001, respectively). Th22 and Th17 cells may contribute to the pathogenesis of GD.     

Peritoneal cavity is dominated by IFNγ-secreting CXCR3+ Th1 cells

The chemokine receptor CXCR3, which was shown to take part in many inflammatory processes, is considered as a Th1 specific marker. Here, we show in a mouse model that CXCR3 expressing CD4(+) cells preferentially migrate to the peritoneal cavity under steady-state conditions. The peritoneal cavity milieu leads to an up-regulated expression of CXCR3. However, blocking of known ligands of this chemokine receptor did not alter the preferential migration. The peritoneal cavity environment also results in an increased percentage of memory cells producing cytokines. Up-regulation of IFNγ production occurs mostly in CXCR3(+) cells considered as Th1, whereas the up-regulation of IL-4 affects mostly in CXCR3(-) cells which are considered as Th2. We conclude that the peritoneal cavity does not change the Th-lineage of the cells, but that domination of this anatomic niche by Th1 cells rather results from preferential migration to this compartment.     

A critical regulation of Th2 cell responses by RORα in allergic asthma

Allergic asthma is a chronic inflammatory disease of the lung and the airway, which is characterized by aberrant type 2 immune responses to otherwise unharmful aeroallergens. While the central role of Th2 cells and type 2 cytokines in the pathogenesis of allergic asthma is well documented, the regulation and plasticity of Th2 cells remain incompletely understood. By using an animal model of allergic asthma in IL-4-reporter mice, we found that Th2 cells in the lung expressed higher levels of Rora than those in the lymph nodes, and that treatment with an RORα agonist SR1078 resulted in diminished Th2 cell responses in vivo. To determine the T cell-intrinsic role of RORα in allergic asthma in vivo, we established T cell-specific RORα-deficient (Cd4creRora^f/f) mice. Upon intranasal allergen challenges, Cd4creRora^f/f mice exhibited a significantly increased Th2 cells in the lungs and the airway and showed an enhanced eosinophilic inflammation compared to littermate control mice. Studies with Foxp3^YFP-creRora^f/f mice and CD8⁺ T cell depletion showed that the increased Th2 cell responses in the Cd4creRora^f/f mice were independent of Treg cells and CD8⁺ T cells. Our findings demonstrate a critical regulatory role of RORα in Th2 cells, which suggest that RORα agonists could be effective for the treatment of allergic diseases.

     

Cytokine Diversity in the Th1-Dominated Human Anti-Influenza Response Caused by Variable Cytokine Expression by Th1 Cells,and a Minor Population of Uncommitted IL-2+IFNγ- Thpp Cells

Within overall Th1-like human memory T cell responses, individual T cells may express only some of the characteristic Th1 cytokines when reactivated. In the Th1-oriented memory response to influenza, we have tested the contributions of two potential mechanisms for this diversity: variable expression of cytokines by a uniform population during activation, or different stable subsets that consistently expressed subsets of the Th1 cytokine pattern. To test for short-term variability, in vitro-stimulated influenza-specific human memory CD4+ T cells were sorted according to IL-2 and IFNγ expression, cultured briefly in vitro, and cytokine patterns measured after restimulation. Cells that were initially IFNγ+ and either IL-2+ or IL-2- converged rapidly, containing similar proportions of IL-2-IFNγ+ and IL-2+IFNγ+ cells after culture and restimulation. Both phenotypes expressed Tbet, and similar patterns of mRNA. Thus variability of IL-2 expression in IFNγ+ cells appeared to be regulated more by short-term variability than by stable differentiated subsets. In contrast, heterogeneous expression of IFNγ in IL-2+ influenza-specific T cells appeared to be due partly to stable T cell subsets. After sorting, culture and restimulation, influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ cells maintained significantly biased ratios of IFNγ+ and IFNγ- cells. IL-2+IFNγ- cells included both Tbet^lo and Tbet^hi cells, and showed more mRNA expression differences with either of the IFNγ+ populations. To test whether IL-2+IFNγ-Tbet^lo cells were Thpp cells (primed but uncommitted memory cells, predominant in responses to protein vaccines), influenza-specific IL-2+IFNγ- and IL-2+IFNγ+ T cells were sorted and cultured in Th1- or Th2-generating conditions. Both cell types yielded IFNγ-secreting cells in Th1 conditions, but only IL-2+IFNγ- cells were able to differentiate into IL-4-producing cells. Thus expression of IL-2 in the anti-influenza response may be regulated mainly by short term variability, whereas different T cell subsets, Th1 and Thpp, may contribute to variability in IFNγ expression.     

Th1／Th2迁移与支气管哮喘研究进展

支气管哮喘是由多种炎症细胞和细胞组分参与的气道慢性炎症疾病。发病机制尚未明了,但作为一种免疫调节异常性疾病已取得大多学者的共识。支气管哮喘是一种Th1／Th2细胞数量及其功能失衡,主要表现为Th2数量及其功能优势的疾病。     

Th1/Th2细胞在心肌梗死中的作用

Th1/Th2细胞因子平衡对于维持机体的正常免疫状态是重要因素,其平衡的紊乱与很多疾病密切相关,如感染性疾病、自身免疫性疾病、肿瘤、心血管疾病等.在心肌梗死的发生发展过程中存在炎症反应,病变的心肌细胞及其他炎症细胞均可产生大量炎症细胞因子和炎症介质,有研究证实这些细胞因子影响心肌重构.近年来关于Th1/Th2细胞因子的平衡与心血管疾病的关系已成为研究的重点.急性心肌梗死的发作与免疫应答的关系越来越引起人们的关注.本文就Th1/rh2细胞在心肌梗死中的作用做一简要综述.     

Th1/Th2细胞分化的分子机制

Th1/Th2细胞亚群的分化是不同的细胞因子、抗原及环境等综合因素作用的结果。在细胞因子参与的Th细胞分化中,JAK/STAT信号途径是细胞因子受体转导细胞内信号的一种主要机制。本文主要就Th1/Th2细胞的功能、分化的分子机制及其影响因素作一综述。     

22. Purification of PVY° and Its Soluble Antigen by Physico Chemical Means

ABSTRACT

Potato virus Y° was purified by centrifugation of infected and minced plant tissue in the virus extraction rotor. As the initial seeding material was heavily contaminated with tobacco mosaic virus (TMV) this virus was isolated and antibody was elicited in chickens. The chicken antibody (IgY) against TMV was used for removing this extraneous virus from the original PVY° seeding material prior to propagating PVY° in tobacco plants, CV Glutinosa.     

Induction of determinant spreading and of Th1 responses by in vitro stimulation with HER-2 peptides

Immunization with tumor antigens induces cellular and humoral immune responses. These responses by T cells are specific for defined epitopes (determinants) in the molecule of the immunizing tumor antigen. Extension of such responses to self-antigens requires induction of autoimmunity to the tumor. As with systems of autoimmune disease, expression of T cell autoimmunity is charaterized by diversification of responses from the inducer determinant to other responder (cryptic) determinants. Since similar strategies may be useful for therapy of human cancers, we investigated whether the induction of response to a HER-2 peptide F7 (776–789) induces enhanced reactivity of other HER-2 peptides. We found that stimulation with F7 can expand a response to another epitope F13 (884–899) in both an ovarian cancer patient with progressive disease and a healthy donor who shared HLA-DR11. This response was characterized mainly by increased interferon γ secretion, and proliferation, but was not observed with another donor who shared HLA-DR14 and HLA-DQ5 with the patient. Since repeated vaccination with the same epitope may lead to a decline of primary cell reactivity caused by apoptosis spreading the response to other epitopes, the tumor antigen may provide an approach for maintaining an inflammatory Th1 response during cancer vaccination. Received: 10 April 2000 / Accepted: 12 July 2000     

乙型肝炎与Th1—Th2细胞失衡的研究进展

根据分泌细胞因子的不同将Ｔｈ细胞分为Ｔｈ０、Ｔｈ１、和Ｔｈ２细胞。Ｔｈ０细胞是Ｔｈ前体细胞,Ｔｈ１细胞促进细胞免疫应答,Ｔｈ２细胞参与体液免疫应答,在感染性疾病中,Ｔｈ１细胞应答抗御感染,Ｔｈ２细胞应答则导致易感。慢性持续性乙型肝炎与Ｔｈ２细胞亚群偏离有关。转基因鼠的研究表明：ＨＢｅＡｇ可选择性诱导Ｔｈ１细胞无反应性,Ｔｈ１－Ｔｈ２细胞亚群失衡受ＴＣＲ－肽－ＭＨＣ复合体及细胞因了环境等多种因素影响     

正确认识Th1—Th2细胞在传染病中的作用

本文对Ｔｈ１及Ｔｈ２细胞在传染病中的作用提出了置疑，认为Ｔｈ１应符保护细胞内寄生病原，Ｔｈ２应答保护细胞外寄生病原体的说法是教条，严重地影响研究的进展。作者认为不应把复杂的免疫学现象简单化。     

An orally active Th1/Th2 balance modulator, M50367, suppresses Th2 differentiation of naïve Th cell in vitro

We previously reported an orally active anti-allergic agent, M50367, modulated Th1/Th2 balance to down-regulate Th2 response in a murine model of atopic asthma. In this study, we examined the effect of M50354, the active metabolite of M50367, on the differentiation of na?ve Th cells into Th1/Th2 cells. M50354 at 3 microM decreased the generation of Th2 cells by 0.2-fold and increased that of Th1 cells by 1.6-fold from na?ve Th cells primed with antigenic peptide and antigen-presenting cells. Its effect was also seen when na?ve Th cells were primed with anti-T cell receptor and anti-CD28 agonistic antibodies instead of antigen and antigen-presenting cells. M50354 decreased early endogenous IL-4 production in the nai;ve Th cell priming culture without affecting interferon-gamma production and proliferation. In contrast, M50354 had no effect on interferon-gamma and IL-4 production from mature Th1 and Th2 cells. These results suggest that M50354 directly acts on na?ve Th cells to suppress their differentiation into Th2 cells.     

弥漫大B细胞淋巴瘤患者Th22细胞及其细胞因子的表达及临床意义

摘要 目的：探讨弥漫大B细胞淋巴瘤（DLBCL）患者辅助性T细胞（Th）22细胞及其细胞因子的表达及临床意义。方法：选择2019年6月到2021年6月河北北方学院附属第一医院收治的121例DLBCL患者（DLBCL组）和70例健康志愿者（对照组）。治疗前、后检测外周血Th22细胞百分比及其细胞因子-白细胞介素（IL）-22、IL-13、 IL-6、肿瘤坏死因子（TNF）-α水平。比较DLBCL组和对照组及不同AnnArbor临床分期、国际预后指数（IPI）评分、Hans免疫分型以及疗效的DLBCL患者外周血Th22百分比及血清IL-22、 IL-13、 IL-6、TNF-α水平差异。结果：DLBCL组外周血Th22细胞百分比、血清IL-22、IL-13、IL-6、TNF-α水平高于对照组（P＜0.05）。Ⅲ～Ⅳ期组、高中危组和高危组、非GCB型组治疗前外周血Th22细胞百分比、血清IL-22、IL-13、IL-6、TNF-α水平分别高于Ｉ～Ⅱ期组、低危组和低中危组、GCB型组（P均＜0.05）。121例患者中判定治疗无效者有39例，根据疗效将患者分为无效组（39例）和有效组（82例），无效组治疗后外周血Th22细胞百分比、血清IL-22、IL-13、IL-6、TNF-α水平与治疗前比较无显著变化（P＞0.05），且无效组治疗前、后高于有效组（P＜0.05）。结论：DLBCL患者外周血中Th22百分比以及血清IL-22、IL-13、IL-6、TNF-α水平升高，且与高AnnArbor临床分期、高IPI评分、非GCB型以及临床治疗效果较差有关。临床可通过监测上述指标水平以调整治疗方案，提高治疗的有效率。     

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。