胃癌患者TH1/TH2漂移的研究

目的观察胃癌病人外周血TH1/TH2细胞及其细胞因子水平的变化,为肿瘤的免疫治疗提供实验依据.方法应用ELISPOT法检测TH1/TH2细胞,ELISA法检测细胞因子.结果胃癌病人TH1细胞及其细胞因子降低,TH2细胞及其细胞因子升高,TH1/TH2比值降低.正常人外周血单个核细胞加IL-12和抗IL-4单抗组,TH1细胞阳性率增加,TH2细胞阳性率降低,TH1/TH2比值升高;加IL-4和抗IFN-γ单抗组TH1细胞阳性率降低,TH2细胞阳性率升高,TH1/TH2比值降低(P＜0.05).结论胃癌病人TH1细胞受抑制,TH2细胞亢进,导致机体的抗肿瘤免疫应答受抑制.利用IL-12诱导TH1细胞的增殖,有可能恢复TH1/TH2平衡.     

胶质瘤细胞中Th1/Th2类细胞因子漂移现象的研究

目的：研究Th1、Th2漂移与脑胶质瘤细胞的发生发展及治疗诊断中作用。方法：采用RT-PCR技术对10株脑胶质瘤细胞进行了IL-4、IL-6、IL-10和TNF-α检测。结果：在脑胶质瘤细胞株中Th2类细胞因子mRNA强势表达，IL-4、IL-5、IL-10和TNF-α的表达率分别为90％(9／10)，70％(70／10)，90％(9／10)，0％(0／10)。结论：肿瘤细胞发生明显的Th2／Tn1漂移现象，造成机体的免疫抑制，有利于肿瘤细胞的免疫逃逸。     

全血培养检测Th1/Th2细胞

目的建立全血培养刺激法检测外周血单核细胞(PBMC)Th1/Th2的方法.方法无菌抽取20名健康检体者静脉血,分别按叶氏和该法(先加入刺激剂全血培养5h后分离淋巴细胞,其余步骤按叶氏报道的免疫组化方法操作)检测Th1/Th2细胞.结果该方法与叶氏法相比,Th1/Th2阳性细胞稍高.结论该方法结果可靠,简便易行,适合临床实验室.     

乙肝病毒宫内感染与TH1／TH2细胞亚群相关研究

乙肝病毒宫内感染是发展成乙肝表面抗原（HBsAg）慢性携带重要原因之一，也是导致生后接种乙肝疫苗失败的主要原因。我国是乙肝高流行区，慢性HBV感染约1．3亿，广西地区占了相当比例。胎儿期的HBV感染，不仅易形成以后慢性携带状态，且是肝硬化和肝癌的高危因素。机体内HBV清除与TH1、TH2型细胞因子有关，细胞因子的不平衡应答能导致乙型肝炎慢性化。因此阻断HBV母婴传播对控制HBV流行具有重要意义。     

Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis

Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-gamma. The role of these cytokines in the pathogenesis of AD is not known. We took advantage of a recently described murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA) (1) and of the availability of mice with targeted deletions of the IL-4, IL-5, and IFN-gamma cytokine genes to assess the role of these cytokines in this model.OVA-sensitized skin from IL-5(-/-) mice had no detectable eosinophils and exhibited decreased epidermal and dermal thickening. Sensitized skin from IL-4(-/-) mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells. These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1beta, and RANTES. Sensitized skin from IFN-gamma-/- mice was characterized by reduced dermal thickening.These results suggest that both the TH2 cytokines IL-4 and IL-5 and the TH1 cytokine IFN-gamma play important roles in the inflammation and hypertrophy of the skin in AD.     

原因不明复发性流产患者血清IL-33水平与TH1、TH2、TH17及Treg细胞间的关系

目的探讨IL-33和T_H1、T_H2、T_H17及调节性T细胞(Treg细胞)在原因不明复发性流产(URSA)患者中的水平及其相关性。方法收集46例URSA患者及40例健康人对照者,流式细胞术检测外周血T_H1、T_H2、T_H17及Treg细胞比例;ELISA检测血清IL-33浓度。结果与健康人对照组相比,URSA患者血清IL-33浓度显著下降,此外,外周血T_H1和T_H17细胞比例更高,而T_H2和Treg细胞则低于健康人对照组(P0.05)。IL-33浓度与T_H1和T_H17细胞比例均显著负相关,而与T_H2细胞比例呈正相关性,但与Treg细胞间无显著相关性(P0.05)。结论 URSA患者外周血IL-33浓度显著下调,并与T_H1、T_H2和T_H17等免疫细胞比例相关,提示在URSA患者中IL-33可能与T_H1、T_H2和T_H17存在关联。     

子宫内膜异位症病人Th1/Th2型细胞因子模式及意义

目的探讨子宫内膜异位症（EM）病人外周血中辅助性T淋巴细胞（Th）1型细胞因子干扰素γ（IFN-γ）及Th2类细胞因子白细胞介素6（IL-6）偏移及其在疾病过程中的意义,从免疫学角度探讨EM的发病机制。方法应用酶联免疫吸附法（ELASA）检测30例EM及20例正常妇女血液IFN-γ及IL-6的水平,并分析Th1/Th2比值变化。结果EM病人血液中IL-6水平与对照组比较显著升高（P〈0.01）;EM病人Ⅲ～Ⅳ期血液中IL-6的水平明显高于Ⅰ～Ⅱ期（P〈0.05）;EM组IFN-γ/IL-6比值明显低于对照组（P〈0.05）,随着临床分期的加重IFN-γ/IL-6比值下降越明显（P〈0.05）。结论EM病人Th2类细胞因子明显增多并占优势漂移的现象,Th1/Th2比值与疾病的分期相关,Th1/Th2细胞因子失衡在EM的发病机制及疾病进展中可能具有重要的作用。     

Induction of B cell apoptosis by TH0, but not TH2, CD4+ T cells.

Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T cell-dependent help. Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen-specific T-B cell interaction, but has also been linked to the induction of B cell apoptosis. To examine the role of T helper cells in either induction of immunoglobulin synthesis or B cell apoptotic death, we have facilitated T cell receptor-MHC interaction through a bacterial superantigen. CD4+ T cell clones could be categorized into two clearly distinct subsets based upon their ability to promote B cell help in the presence of superantigen. One subset of T cell clones supported immunoglobulin synthesis, and thus functioned as effective helper cells. B cells interacting with the second subset of T cells did not differentiate into antibody-secreting cells, but underwent apoptosis. Both types of helper cells were able to provide contact help after anti-CD3 stimulation. Induction of apoptosis was a dominant phenomenon; the addition of the superantigen suppressed immunoglobulin production in B cells activated by anti-CD3-stimulated helper T cells, indicating that the T cells delivered an apoptotic signal to the B cell. T cell clones providing effective MHC restrictive B cell help could be distinguished from T cells facilitating B cell apoptosis based on their lymphokine secretion profile. Induction of B cell apoptosis was a feature of T cells with a TH0 lymphokine pattern. Promotion of MHC-restricted B cell help was associated with a TH2 lymphokine profile. TH1-derived cytokines alone could not substitute for apoptosis-inducing T cells.     

1975 Interstate postgraduate medical assembly 60TH Program

Observed platelet changes in women known to be taking oral contraceptives prompted a study to see whether estrogen users could be identified solely by examination of Wright-stained blood smears. The examiner correctly identified as estrogen users all of a group of 26 women who were taking an oral contraceptive containing estrogen and progesterone.     

Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle

CD4(+) T helper (TH)1- and TH2-type cytokines reportedly play an important role in the pathobiology of asthma. Recent evidence suggests that proasthmatic changes in airway smooth muscle (ASM) responsiveness may be induced by the autocrine release of certain proinflammatory cytokines by the ASM itself. We examined whether TH1- and TH2-type cytokines are expressed by atopic asthmatic sensitized ASM and serve to autologously regulate the proasthmatic phenotype in the sensitized ASM. Expression of these cytokines and their receptors was examined in isolated rabbit and human ASM tissues and cultured cells passively sensitized with sera from atopic asthmatic patients or control subjects. Relative to controls, atopic sensitized ASM cells exhibited an early increased mRNA expression of the TH2-type cytokines, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and their receptors. This was later followed by enhanced mRNA expression of the TH1-type cytokines, IL-2, IL-12, and interferon-gamma (IFN-gamma), as well as their respective receptors. In experiments on isolated ASM tissue segments (a) exogenous administration of IL-2 and IFN-gamma to atopic asthmatic serum-sensitized ASM ablated both their enhanced constrictor responsiveness to acetylcholine (ACh) and their attenuated relaxation responsiveness to beta-adrenoceptor stimulation with isoproterenol, and (b) administration of IL-5 and GM-CSF to naive ASM induced significant increases in their contractility to ACh and impaired their relaxant responsiveness to isoproterenol. Collectively, these observations provide new evidence demonstrating that human ASM endogenously expresses both TH1- and TH2-type cytokines and their receptors, that these molecules are sequentially upregulated in the atopic asthmatic sensitized state, and that they act to downregulate and upregulate proasthmatic perturbations in ASM responsiveness, respectively.     

Flt-3 ligand as adjuvant for DNA vaccination augments immune responses but does not skew TH1/TH2 polarization

Since transfection of dendritic cells (DC) plays a key role in DNA vaccination, in vivo expansion of DC might be a tool to increase vaccine efficacy. We asked whether Fms-like tyrosine kinase-3 ligand (Flt-3L), a growth factor for DC, can be used as an adjuvant for DNA vaccination. Beta-galactosidase (beta-gal) was used as a model antigen in C57BL/6 mice. Mice were immunized i.m. with DNA coding for beta-gal with or without additional injection of Flt-3L. In both cases, antigen-specific CD4+ and CD8+ T cells were detectable after vaccination. Compared with DNA alone, additional administration of Flt-3L led to a significant increase in the antigen-specific proliferative response. However, increased cytotoxicity by T cells was not observed. The cytokines secreted by splenocytes of immunized mice upon in vitro stimulation with antigen had a TH2 profile. Humoral responses against beta-gal preferentially consisted of IgG1 antibodies. Analysis of DC from Flt-3L-treated mice revealed an immature phenotype with low or absent expression levels of CD80, CD86 and CD40. We conclude that Flt-3L does not generally skew immune responses towards a TH1 type. More likely, factors determined by the antigen and/or the vaccination procedure itself are crucial for the resulting type of immune response. Flt-3L - under circumstances such as the one we have investigated - can also lead to suppression of TH1 T cell immunity, possibly by expansion of immature/unactivated DC.     

阿德福韦酯对慢性乙型肝炎患者Th1/Th2型细胞因子和肝纤维化指标的影响

目的探讨阿德福韦酯抗病毒治疗对慢性乙型肝炎患者肝纤维化的临床疗效及对外周血Thl/Th2细胞因子的影响。方法将60例慢性乙型肝炎患者随机分为治疗组和对照组,各30例。治疗组患者给予口服阿德福韦酯10 mg/次/d,共同48周,对照组采用常规治疗方法。采用放射免疫法测定2组患者治疗前后血清中肝纤维化指标HA、ⅣC、PCIII和LN的水平;采用DAS ELISA法检测2组患者治疗前后血清中细胞因子IFN-γ、IL-4水平。结果治疗组与对照组治疗前各项血清肝纤维化指标和血清中细胞因子IFN-γ、IL-4水平差异无统计学意义(P0.05);2组治疗后血清各项肝纤维化指标和细胞因子IFN-γ、IL-4水平差异有统计学意义(P0.01)。结论慢性乙型肝炎患者外周血Th1/Th2细胞因子的水平与肝纤维化指标密切相关。阿德福韦酯除直接抑制病毒作用外,还可能通过免疫调节作用抑制病毒复制。