哮喘患者外周血Treg和Th1/Th2的变化及其与哮喘病情的关系

目的：探讨哮喘患者外周血调节性T细胞（Treg）以及辅助性T细胞（Th1/Th2）的比例的变化,探讨其在哮喘的临床治疗中的作用。方法：80例哮喘患者（哮喘组）按临床表现分为急性发作期组（54例）和缓解期组（26例）,同时选择50例健康体检者。应用流式细胞仪检测上述各组外周血CD4＋CD25＋Foxp3＋Treg、CD4＋IFN-γ＋Th1和CD4＋IL-4＋Th2细胞水平,并进行统计学分析。结果：哮喘组CD4＋CD25＋Foxp3＋Treg水平亦明显低于正常对照组（P〈0.05。其中急性发作期组Treg水平明显低于缓解期组和正常对照组（P〈0.05）。而哮喘组Th1/Th2比值显著低于对照组（P〈0.05）,且在哮喘急性发作组中Th1/Th2比值显著低于缓解期组和正常对照组（P〈0.05）。结论：提示Treg和Th在哮喘的发生和发展中起着重要的作用。     

人类免疫缺陷病毒1型同性恋感染者与健康人群Th17/Treg平衡状况的比较研究

通过探讨人类免疫缺陷病毒1型(HIV-1)同性恋感染者外周血中辅助性T细胞17(Th17)与CD4+CD25hiFoxp3+调节性T细胞(Treg)比例及Th17/Treg平衡状态与疾病进展的关系,初步阐明Th17/Treg失衡在HIV发病机制中的作用和意义。选取54例未经抗病毒治疗的HIV感染者,另有32名健康志愿者作为正常对照。分离外周血单核细胞后,利用流式细胞技术检测Th17和Treg水平。结果表明,在HIV感染者外周血中Th17比例明显低于正常对照组(0.68±0.35vs1.42±0.86,P<0.001),Treg比例明显高于正常对照(6.15±2.12vs4.50±0.76,P<0.001),导致HIV感染者中Th17/Treg比例较正常对照显著降低(0.12±0.07vs0.31±0.17,P<0.001)。研究还发现,Th17/CD4比例与CD4+T细胞计数正相关(r=0.371,P<0.05),与病毒载量不相关;Treg/CD4比例与CD4+T细胞计数负相关,与病毒载量正相关(r=-0.402,P<0.05;r=0.447,P<0.001)。此外,Th17/Treg比例与CD4+T细胞计数正相关,与病毒载量负相关(r=0.525,P<0.001;r=-0.318,P<0.05)。结果提示,HIV感染中存在Th17/Treg失衡现象,与疾病进程密切相关,可能在HIV进展中具有重要作用。     

急性发作支气管哮喘患儿粪便菌群特征及其与Th17细胞免疫功能的关系CSCD

目的 研究急性发作支气管哮喘儿童粪便菌群特征及其与Th17细胞免疫功能的关系,为该类患儿的治疗提供参考。方法 选择2019年12月至2020年12月我院收治的96例急性发作支气管哮喘患儿为研究组,选择同期来我院进行粪便检查并结果正常的60例健康体检儿童为对照组。对比两组对象粪便菌群分布情况,外周血TGF-β_(1)、IL-17、Th17细胞、Treg细胞、Th17/Treg水平。采用Pearson相关分析患儿粪便菌群数量与Th17细胞免疫功能的相关性。结果 研究组患儿粪便中大肠埃希菌数量显著高于对照组,而乳杆菌和双歧杆菌数量显著低于对照组(均P<0.05)。研究组患儿外周血TGF-β_(1)、 IL-17、 Th17细胞、Th17/Treg水平显著高于对照组,而Treg细胞水平显著低于对照组(均P<0.05)。Pearson相关分析表明,哮喘患儿粪便大肠埃希菌数量与外周血TGF-β_(1)、 IL-17、 Th17细胞、 Th17/Treg水平呈正相关(r=0.528、0.714、0.524、0.572,均P<0.05),与外周血Treg细胞水平呈负相关(r=-0.439,P<0.05)。哮喘患儿粪便乳杆菌数量与外周血Treg细胞水平呈正相关(r=0.459, P<0.05),与外周血TGF-β_(1)、 IL-17、 Th17细胞、Th17/Treg水平呈负相关(r=-0.457、-0.692、-0.491、-0.563,均P<0.05)。哮喘患儿粪便双歧杆菌数量与外周血Treg细胞水平呈正相关(r=0.462,P<0.05),与外周血TGF-β_(1)、IL-17、Th17细胞、Th17/Treg水平呈负相关(r=-0.496、-0.729、-0.542、-0.558,均P<0.05)。结论 急性发作支气管哮喘患儿肠道优势菌数量减少,肠道机会致病菌数量增加,并与Th17细胞免疫功能存在一定联系。     

分泌性中耳炎患者外周血Th1Th2细胞及T淋巴细胞亚群水平的表达及临床意义

目的:探讨分泌性中耳炎(SOM)患者外周血T辅助细胞1(Th1)、T辅助细胞2(Th2)细胞因子及T淋巴细胞亚群水平的表达及其临床意义。方法:选取我院于2015年1月至2018年1月期间收治的SOM患者135例记为SOM组,根据病程将患者分为急性组(病程14d,49例)、亚急性组(病程14-30d,53例)、慢性组(病程30d,33例)。另外选择同期于我院进行体检的100例健康者为对照组。分别对比SOM组和对照组受试者、不同病程SOM患者外周血Th1细胞因子[干扰素(INF-γ)、白细胞介素-2(IL-2)]、Th2细胞因子[白细胞介素-4(IL-4)、白细胞介素-10(IL-10)]以及T淋巴细胞亚群[CD3~+、CD4~+、CD8~+、CD4~+/CD8~+]水平。采用Pearson相关性分析INF-γ、IL-2、IL-4、IL-10与CD3~+、CD4~+、CD8~+、CD4~+/CD8~+的相关性。结果:SOM组患者外周血INF-γ、IL-2、IL-4、IL-10水平高于对照组(P0.05);急性组患者外周血INF-γ、IL-2、IL-4、IL-10水平低于亚急性组、慢性组,亚急性组患者外周血INF-γ、IL-2、IL-4、IL-10水平低于慢性组(P0.05)。SOM组患者外周血CD3~+、CD4~+、CD4~+/CD8~+水平低于对照组,CD8~+水平高于对照组(P0.05);急性组患者外周血CD3~+、CD4~+、CD4~+/CD8~+水平高于亚急性组、慢性组,CD8~+水平低于亚急性组、慢性组,亚急性组患者外周血CD3~+、CD4~+、CD4~+/CD8~+水平高于慢性组,CD8~+水平低于慢性组(P0.05)。Pearson相关性分析结果显示,SOM患者外周血INF-γ、IL-4与CD8~+呈正相关(P0.05),IL-4与CD3~+、CD4~+呈负相关(P0.05)。结论:SOM患者外周血Th1Th2细胞因子、T淋巴细胞亚群水平均表现异常,且其水平与疾病发生和发展存在一定联系,通过监测Th1Th2细胞因子、T淋巴细胞亚群有助于评估SOM患者病情。     

晚期非小细胞肺癌患者外周血Th17细胞和Treg细胞水平与化疗敏感相关性研究

目的:探讨晚期非小细胞肺癌患者外周血Th17细胞和Treg细胞水平和化疗敏感性相关性。方法:2选取78例晚期非小细胞肺癌患者为病例组,同时纳入健康人群40例为对照组。病例组肺癌患者采用TP方案,化疗前后采用流式细胞计数检测外周血Th17(CD4~+γ-IFN~+)、Treg(CD4~+CD25~+Foxp3~+)水平,完成2个化疗疗程后,评价化疗效果及敏感性。结果:病例组外周血Th17细胞和Treg细胞水平明显高于对照组,差异有统计学意义(p0.05)。病例组第一次和第二次化疗前外周血Th17细胞和Treg细胞水平高于化疗后水平,差异有统计学意义(p0.05)。根据WHO实体肿瘤化疗效果判定标准,CR为化疗敏感组、PR、SD为化疗有效,PD为化疗无效,将所有病例组分为化疗敏感性组、有效组和无效。第一次化疗前和第二次化疗前外周血Th17细胞和Treg细胞水平,化疗敏感组水平明显高于有效组和无效组,而有效组水平高于无效组,差异有统计学意义(p0.05)。结论:肺癌患者晚期外周血Th17细胞和Treg细胞水平明显升高,其Th17细胞和Treg细胞水平和化疗敏感性呈正相关的趋势。     

调节性T 细胞在发热结缔组织病患者外周血中的表达及临床意义

目的:研究Treg细胞在发热CTD患者外周血表达对结核感染的诊断价值。方法:对103例发热CTD患者进行T-SPOT.TB试验,将39例阳性者设为实验组-1,进行抗结核治疗,将64例阳性者设为实验组-2,另选取40例健康者作为对照组,检测三组外周血CD4+CD25+Treg细胞、Foxp3基因、IL-10、TGF-β的表达。结果:实验组CD4+CD25+Foxp3 Treg细胞占CD4+T比例高于对照组(P0.05),实验组-1治疗前外周血CD4+CD25+Foxp3 Treg细胞占CD4+T比例高于实验组-1治疗后、实验组-2(P0.05);实验组TGF-β表达量低于对照组(P0.05),实验组-1治疗前低于实验组-1治疗后及实验组-2(P0.05);实验组-1治疗前IL-10表达量低于实验组-1治疗后、实验组-2及对照组(P0.05)。结论:CD4+CD25+Foxp3 Treg细胞在发热CTD伴有结核感染患者外周血中的表达升高,其变化可作为结核感染诊断的辅助性指标。     

老年COPD疾病进展与机体调节性T 细胞的关系分析

目的:探讨老年慢性阻塞性肺疾病(COPD)患者疾病进展与机体调节性T细胞(Treg)的关系。方法:选取我院收治的65例COPD患者(COPD组)以及同期在我院行体检的健康人群45例(正常对照组),将COPD患者分为急性期组41例及稳定期组24例,采用肺功能仪检测肺功能,采用酶联免疫吸附法检测血清γ-干扰素(IFN-γ)、白介素4(IL-4)、IL-17水平,采用流式细胞仪检测外周血CD4+CD25+Treg细胞比例。结果:与正常对照组比较,COPD患者的FEV1、FVC、PEF、FEV1/FVC、6MWT、血清IL-4水平、外周血CD4~+CD25~+Treg细胞比例均明显下降,血清IFN-γ、IL-17及Th1/Th2均显著升高。急性期COPD患者的CD4~+CD25~+Treg细胞比例较正常对照组显著升高,而正常对照组患者的CD4~+CD25~+Treg细胞比例较稳定组COPD患者显著升高,组间比较均有明显差异(P0.05)。结论:老年CODP患者体内存在免疫功能失调,调节性T细胞可能参与了老年COPD疾病的发病以及急性加重过程,导致患者出现肺功能改变。     

消化道肿瘤患者外周血调节性T细胞的变化及其意义

目的:通过测定外周血CD4+CD25+Foxp3+调节性T(Treg)细胞比例,探讨其与消化道肿瘤发生、发展的关系.方法:采用流式细胞术(FCM)检测156例消化道恶性肿瘤患者(消化道恶性肿瘤组)与50名健康体检者(对照组)的外周血中CD4+CD25+Foxp3+Treg细胞的水平,并进行比较分析.结果:消化道肿瘤患者CD4+CD25+Foxp3+Treg比例明显高于对照组(P<0.01),且随疾病进展恶性肿瘤患者外周血CD4+CD25+Foxp3+Treg细胞的比例升高.结论:CD4+CD25+Foxp3+Treg在消化道肿瘤患者外周血中比例升高,提示其可能是癌症患者细胞免疫功能削弱的机制之一,与消化道肿瘤的发生和发展密切相关.     

哮喘患者诱导痰和外周血CD3+CD56+NKT 细胞的检测及意义

目的:研究CD3+CD56+NKT细胞在哮喘患者急性发作期诱导痰和外周血中的比例改变,并探讨其临床意义.方法:以28例哮喘急性发作期患者为研究组,22名正常人作为对照组,采用二色直接荧光素标记法和多参数流式细胞仪检测诱导痰和外周血CD3+CD56+NKT细胞的比例,同时检测外周血IL-4、Ig-E及INF-γ等水平.结果:哮喘患者急性发作期诱导痰和外用血CD3+CD56+NKT细胞明显高于健康对照组(P<0.01).哮喘患者急性发作期外周血IL-4、Ig-E及INF-γ等水平明显高于健康对照组(P<0.05).哮喘患者外周血中CD3+CD56+NKT细胞比例与IL-4、Ig-E及INF-γ升高成正相关.结论:哮喘患者急性发作期诱导痰和外周血中的CD3+CD56+NKT细胞明显增高,CD3+CD56+NKT细胞可能通过调节IL-4、Ig-E及INF-γ等细胞因子从而在哮喘的发病机制发挥重要作用.     

慢性阻塞性肺疾病患者外周血CD4+CD25+CD127(Low/-)调节性T细胞的检测及临床意义

目的:研究CD4+CD25+CD127(Low/-)节性T细胞在慢性阻塞性肺疾病(COPD)急性发作期外周血中的比例改变及其临床意义.方法:以25例COPD急性发作期患者外周血为研究组,20名正常人外周血作为对照组,采用三色直接荧光素标记法和多参数流式细胞仪检测外周血CD4+CD25+CD127(Low/-)调节性T细胞的比例,同时检测外周血C-反应蛋白(CRP)、血沉(ESR)、免疫球蛋白(Ig)等水平.结果:COPD急性发作期患者外周血CD4+CD25+CD127(Low/-)调节性T细胞占外周血CD4+淋巴细胞的比例明显低于健康对照组(P＜0.01).而COPD急性发作期患者外周血CRP、ESR、Ig等水平明显高于健康对照组(P＜0.05).COPD患者外周血调节T细胞下降与CRP和IgG升高成负相关.结论:COPD患者外周血CD4+CD25+CD127(Low/-)调节性T细胞在CD4+T淋巴细胞的比例明显减少,调节性T细胞等免疫调节因素可能在COPD的发病机制发挥重要作用.     

心衰病人的血清T3,T4测定及其意义

目的探讨心衰患者血清Ｔ３、Ｔ４的含量及其临床意义。方法应用放射免疫法测定心衰患者血清Ｔ３、Ｔ４水平５０例,并与３０例病因基本相同心功能代偿者作对照。结果重度心衰者Ｔ３、Ｔ４水平明显下降,与对照组对比差异有显著性（Ｐ＜０．０５）。结论血清Ｔ３、Ｔ４水平与病人预后密切相关,可作为判断病人病情严重程度及临床疗效的综合指标之一。     

Inflammasomes in T cells

The concept of non-self recognition through germ-line encoded pattern recognition receptors (PRRs) has been well-established for professional innate immune cells. However, there is growing evidence that also T cells employ PRRs and associated effector functions in response to certain non-self or damage signals. Inflammasomes constitute a special subgroup of PRRs that is hardwired to a signaling cascade that culminates in the activation of caspase-1. Active caspase-1 processes pro-inflammatory cytokines of the IL-1 family and also triggers a lytic programmed cell death pathway known as pyroptosis. An increasing body of literature suggests that inflammasomes are also functional in T cells. On the one hand, conventional inflammasome signaling cascades have been described that operate similarly to pathways characterized in innate immune cells. On the other hand, unconventional functions have been suggested, in which certain inflammasome components play a role in unrelated processes, such as cell fate decisions and functions of T helper cells. In this review, we discuss our current knowledge on inflammasome functions in T cells and the biological implications of these findings for health and disease.     

Structural chromosome differentiation between Triticum timopheevii and T. turgidum and T. aestivum

 Chromosome pairing at metaphase-I was analyzed in F₁ hybrids among T. turgidum (AABB), T. aestivum (AABBDD), and T. timopheevii (A^tA^tGG) to study the chromosome structure of T. timopheevii relative to durum (T. turgidum) and bread (T. aestivum) wheats. Individual chromosomes and their arms were identified by means of C-banding. Homologous pairing between the A-genome chromosomes was similar in the three hybrid types AA^tBG, AA^tBGD, and AABBD. However, associations of B-G were less frequent than B-B. Homoeologous associations were also observed, especially in the AA^tBGD hybrids. T. timopheevii chromosomes 1A^t, 2A^t, 5A^t, 7A^t, 2G, 3G, 5G, and 6G do not differ structurally from their counterpart in the A and B genomes. Thus, these three polyploid species inherited translocation 5AL/4AL from the diploid A-genome donor. Chromosome rearrangements that occurred at the tetraploid level were different in T. turgidum and T. timopheevii. Translocation 4AL/7BS and a pericentric inversion of chromosome 4A originated only in the T. turgidum lineage. The two lines of T. timophevii studied carry four different translocations, 6A^tS/1GS, 1GS/4GS, 4GS/4A^tL, and 4A^tL/3A^tL, which most likely arose in that sequence. These structural differences support a diphyletic origin of polyploid wheats. Received: 15 June 1998 / Accepted: 19 August 1998     

Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells

Naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) suppress proliferation of CD4(+)CD25(-) effector T cells (Teffs) by mechanisms that are not well understood. We have previously demonstrated a novel mechanism of Treg suppression, i.e. interference with extracellular redox remodeling that occurs during activation of T cells by dendritic cells. In this study, we demonstrate that Treg-mediated redox perturbation is antigen-dependent but not antigen-specific, is CTLA-4-dependent, and requires cell-cell contact. Furthermore, we show that Tregs use multiple strategies for extracellular redox remodeling, including diminished GSH synthesis in dendritic cells via decreased expression of γ-glutamylcysteine synthetase, the limiting enzyme for GSH synthesis. Tregs also consume extracellular cysteine and partition it more proficiently to the oxidation product (sulfate), whereas Teffs divert more of the cysteine pool toward protein and GSH synthesis. Tregs appear to block GSH redistribution from the nucleus to the cytoplasm in Teffs, which is abrogated by the addition of exogenous cysteine. Together, these data provide novel insights into modulation of sulfur-based redox metabolism by Tregs, leading to suppression of T cell activation and proliferation.     

以T细胞受体为基础的免疫疗法研究进展

T细胞是机体抗肿瘤免疫的核心,以T细胞功能调控为基础的免疫检查点疗法已经在多种肿瘤的临床治疗中取得了重大突破,以基因工程化T细胞为基础的过继性免疫细胞疗法在血液瘤治疗中取得了重要进展,免疫治疗已经对肿瘤的临床治疗产生了深刻变革,成为肿瘤临床治疗策略的重要组成部分。T细胞受体（T cell receptor,TCR）赋予了T细胞识别肿瘤抗原的特异性,能够识别由主要组织相容性复合体（major histocompatibility complex,MHC）呈递的包括胞内抗原在内的广泛肿瘤抗原,具有高度的抗原敏感性,因而具有广泛的抗肿瘤应用前景。2022年第一款TCR药物的上市开启了TCR药物开发的新纪元,多项TCR药物临床研究表现出潜在的肿瘤治疗价值。本文综述了以TCR为基础的免疫治疗策略研究进展,包括T细胞受体工程化T细胞（T cell receptor-engineered T cell,TCR-T）和TCR蛋白药物,以及基于TCR信号的其他免疫细胞疗法,以期为以TCR为基础的免疫治疗策略开发提供参考。     

Vdelta1+ T cells are crucial for repertoire formation of gammadelta T cells in the lung

The pulmonary resident T lymphocytes (RPLs) expressing a nearly invariant T cell receptor γδ heterodimer (γδTCR) migrate from fetal thymus to the lung epithlium, followed by RPL subsets expressing diverse sets of γδTCRs after birth. However, it remains unclear whether the fetal type Vγ6/Vδ1⁺ RPLs are essential for γδ T cell repertoire formation in the lung epithelium. In this study, we found a marked decrease in the number of γδRPLs at 4 weeks of age in Vδ1^−/− mice and they predominantly expressed Vγ6 and Vδ4 genes. The skewed diversity towards the Vδ4-(Dδ1)-Dδ2-Jδ2 junctional region was observed only in γδ RPLs from 4-week-old Vδ1^−/− mice, compared with those from 8-week-old Vδ1^−/− mice and the both ages of wild-type mice. These results suggest that the invariant Vδ1⁺ T cells are crucial not only for optimal γδ T cell expansion but also for affecting the migration or microenvironment for other γδ T cells in the lung epithelium.     

Changes of frequency and expression level of CD161 in CD8+ T cells and natural killer T cells in peripheral blood of patients with systemic lupus erythematosus

Immunologic abnormalities of natural killer (NK) cells and T cells play a role in the pathogenesis of systemic lupus erythematosus (SLE). CD161 is expressed on most of the NK cells and on some T cells. The quantities of CD161-expressing cells and expression levels of CD161 were analyzed in T cells and NK cells from patients with SLE compared with normal controls. The expression of CD161 on NK cells, NKT cells, CD4⁺ T cells, and CD8⁺ T cells in peripheral blood from patients with inactive SLE and active SLE, and from the normal controls group were determined using flow cytometry. The frequency and expression level of CD161 in the lymphocyte subsets and its relationship with the quantity of regulatory T cells, anti-double stranded DNA antibody, and the titer of antinuclear antibody were evaluated. Both the percentages of the CD161⁺ subpopulation and the mean fluorescence intensities (MFIs) of CD161 in CD8⁺ T cells and NKT cells decreased significantly in SLE patients compared with normal controls (P < .001). The CD161 expression in CD8⁺ T cells and NKT cells also decreased in the anti-dsDNA (+) group (P < .05). The counts of Treg cells were lower in SLE patients and were weakly correlated with the percentage of the CD161 subpopulation (r = 0.229, P = .016) and the MFIs of CD161 expression in CD8⁺ T cells (r = .232, P = .014). The frequencies and levels of CD161 expression on CD8⁺ T cells and NKT cells were reduced in SLE patients, suggesting that an abnormality of these cells was related to the pathogenesis of SLE.