Whether vitamin A supplementation is effective in T-bet and IFN-ɣ gene expression reduction?

Background: The aim of present study is evaluation of vitamin A supplementation efficacy on IFN-? and T-bet gene expression in atherosclerotic patients.

Methods: Thirty-one patients and 15 healthy controls participated in this study. Healthy control and patients in Vitamin A group received 25?000?IU retinyl palmitate daily for 4 months. Control patients also received 1 pearl of placebo per day up to 4 months. Gene expression levels were assessed by real-time PCR using SYBR green detection method.

Results: IFN-γ gene expression in fresh cells of patients taking vitamin A declined slightly (0.85-fold, p?=?0.068), whereas the expression of this gene was increased in patients taking placebo, and in healthy control subjects 1.2-fold (p?=?0.267) and 1.7-fold (p?=?0.580), respectively. There were no significant difference (p?=?0.159) between 3 groups in terms of IFN-γ gene expression in cells stimulated with PHA. In order to determine whether PHA stimulation of PBMCs in vitro had an effect on T-bet expression, we measured the difference between the 3 groups of studied. The results showed significant differences between the groups (p?=?0.046). IFN-γ gene expression in cells activated with ox-LDL in healthy control subjects and patients taking vitamin A, was reduced 0.43 (p?=?0.0001) and 0.41 (p?=?0.001) respectively, but in placebo patients was increased 2.2-fold (p?=?0.959).

Conclusion: Considering role of vitamin A on suppression of Th1 cells in atherosclerotic patients, it can be concluded that vitamin A supplementation may be advantageous for these patients.     

Interferon gamma enhances both in vitro and in vivo priming of CD4+ T cells for IL-4 production

Classical studies have demonstrated that in vitro priming of naive CD4 T cells to become T helper (Th)2 cells is strikingly dependent on interleukin (IL)-4, whereas priming for interferon (IFN)gamma production is IL-12/IFNgamma-dependent. Therefore, it was quite surprising when we noted that priming of naive C57BL/6 CD4(+) cells to become IL-4 producers was substantially inhibited by the addition of anti-IFNgamma antibodies. This was true using immobilized anti-CD3 and anti-CD28 antibodies or soluble anti-CD3/anti-CD28 and antigen-presenting cells in the presence or absence of added IL-4. Priming of CD4 T cells from IFNgamma(-/-) C57BL/6 mice with immobilized anti-CD3 and anti-CD28 resulted in limited production of IL-4, even with the addition of 1,000 U/ml of IL-4. Titrating IFNgamma into such cultures showed a striking increase in the proportion of T cells that secreted IL-4 upon challenge; this effect was completely IL-4-dependent in that it was blocked with anti-IL-4 antibody. Thus, IFNgamma plays an unanticipated but substantial role in Th2 priming, although it is an important Th1 cytokine, and under certain circumstances a Th1 inducer.     

Eliminating roles for T-bet and IL-2 but revealing superior activation and proliferation as mechanisms underpinning dominance of regulatory T cells in tumors

Foxp3⁺ regulatory T cells (Tregs) are often highly enriched within the tumor-infiltrating T cell pool. Using a well-characterised model of carcinogen-induced fibrosarcomas we show that the enriched tumor-infiltrating Treg population comprises largely of CXCR3⁺ T-bet⁺ ‘T_H1-like’ Tregs which are thymus-derived Helios⁺ cells. Whilst IL-2 maintains homeostatic ratios of Tregs in lymphoid organs, we found that the perturbation in Treg frequencies in tumors is IL-2 independent. Moreover, we show that the T_H1 phenotype of tumor-infiltrating Tregs is dispensable for their ability to influence tumor progression. We did however find that unlike Tconvs, the majority of intra-tumoral Tregs express the activation markers CD69, CD25, ICOS, CD103 and CTLA4 and are significantly more proliferative than Tconvs. Moreover, we have found that CD69⁺ Tregs are more suppressive than their CD69⁻ counterparts. Collectively, these data indicate superior activation of Tregs in the tumor microenvironment, promoting their suppressive ability and selective proliferation at this site.     

老年非小细胞肺癌患者Th1/Th2漂移状态与T-bet/GATA3基因表达的关系

目的探讨老年非小细胞肺癌患者Th1/Th2漂移状态及其与T-bet、GATA3基因表达的关系。方法选取老年非小细胞肺癌患者及健康受试者各120例,双抗夹心酶联免疫吸附测定(ELISA)方法检测各组血浆中Th1类细胞因子γ干扰素(IFN-γ)、白细胞介素-2(IL-2)和Th2类细胞因子IL-4、IL-10的浓度;梯度离心法分离出单个核细胞(PB-MC),采用RT-PCR方法检测其T-bet、GATA3mRNA水平。结果老年非小细胞肺癌患者Th1型细胞因子IFN-γ、IL-2水平与老年健康受试者比较明显下降[(10.28±0.88)pg/mL vs(16.94±1.05)pg/mL;(9.06±0.85)pg/mL vs(13.96±0.87)pg/mL)],差异均具有统计学意义;老年非小细胞肺癌患者Th2型细胞因子IL-4、IL-10水平与老年健康受试者比较明显升高[(5.98±0.98)pg/mL vs(3.89±0.28)pg/mL;(47.59±2.89)pg/mL vs(40.47±1.28)pg/mL)],差异均具有统计学意义。老年非小细胞肺癌患者Th1型核转录因子T-bet mRNA的表达水平较老年健康受试者下降[(0.85±0.11)vs(1.46±0.09)];老年非小细胞肺癌患者Th2型核转录因子GATA3mRNA的表达水平较老年健康受试者明显增高[(1.51±0.12)vs(0.89±0.10)],差异均具有统计学意义。结论老年非小细胞肺癌患者存在着Th2漂移现象,该现象可能与影响Th1/Th2的极化状态的关键因子T-bet和GATA3的表达失常有关。     

再生障碍性贫血患者外周血T-bet和GATA-3转录因子基因表达失衡的分析

目的探讨再生障碍性贫血(aplastic anemia,AA)患者外周血单个核细胞中T-bet/GATA-3的比率与Th1/Th2细胞失衡的关系。方法采用RT-PCR法检测30例初诊AA患者及20名健康人外周血单个核细胞(PBMC)转录因子T-bet、GATA-3 mRNA的表达水平,ELISA法检测血浆IFN-γ和IL-4水平。结果 AA组PBMC中T-bet mRNA及血浆IFN-γ水平均显著高于正常对照组(P分别<0.01),且T-bet/GATA-3 mRNA的比率较对照组明显升高(P<0.01),Th1类细胞因子IFN-γ的水平与T-bet/GATA-3的比率成正相关(r=0.84),而Th2类细胞因子IL-4的水平降低,与T-bet/GATA-3的比率成负相关(r=0.75)。结论 T-bet和IFN-γ表达的增高在AA的发病中可能起到重要作用;AA患者T-bet/GATA-3的比率升高可作为评价Th1/Th2细胞失衡的另一重要指标,在协助临床对AA诊断中起重要作用。     

T效应细胞通路在哮喘发病机制中的研究进展及靶向治疗前景

哮喘是儿童常见的慢性气道炎症疾病,以气道变异性炎症和高反应性为特点,对哮喘发病机制的研究,从最初的TH1/TH2范围,已扩展至T调节细胞及促炎症TH17细胞系,转录因子T-bet(TH1)、GATA-3(TH2)、FOXP3(Treg)、RORγτ/RORα(TH17)参与各T细胞亚群分化发展及之间的交叉调节,可能成为哮喘临床治疗潜在的药物靶向点。     

川崎病患儿细胞免疫功能状况及转录因子T-bet和GATA3的调控作用*

 目的： 研究川崎病患儿细胞免疫功能状况及转录因子T-bet和GATA3的调控作用。方法: 选取41 例川崎病患儿为研究对象,同时选取年龄和性别相匹配的因急性上呼吸道感染发热儿童40例为对照组,分别采用三色荧光流式细胞术和半定量逆转录-聚合酶链反应检测2组患儿外周血Th1、Th2细胞数量及单个核细胞中T-bet和GATA3 mRNA水平。结果: 川崎病患儿外周血Th1、Th2细胞比率及单个核细胞转录因子T-bet mRNA、GATA3 mRNA转录水平分别为(10.36±3.69)%、(6.46±2.28)%、0.51±0.16和0.38±0.13,均显著低于对照组［(25.26±5.22)%、(16.87±4.35)%、0.62±0.21和0.46±0.12,P<0.05］。Spearman相关分析显示Th1和Th2细胞比率分别与T-bet mRNA和GATA3 mRNA水平呈正相关。结论: 川崎病患儿急性期T细胞并非活化而是处于抑制状态,T-bet和GATA3分别对Th1和Th2细胞增殖具有调控作用。