初发系统性红斑狼疮患者Th1/Th2及其调控因子IL-10 IL-12基因研究

目的：探讨初发系统性红斑狼疮（SLE）病人Th1/Th2分布及其调控细胞因子、细胞因子受体基因表达的差异。方法：运用三色荧光标记法流工细胞术检测42例未红药物治疗初发狼疮病人，T细胞亚群分布，并以10名正常人作对照；同时运用ABI－7700实时监测定量PCR法检测其中38例病人和28名正常人IL－10／IL－12 mRNA及其受体表达的差异。结果：①初发SLE病人Th1较正常人明显减低（P＜0．05）；但Th1/Th2无显著性改变。②与正常组相比，SLE组病人IL－10mRNA表达差异无显著性，但IL－10R表达明显升高（P＜0．05）；SLE组病人IL－12mRNA及其受体表达较正常人明显降低（P均＜0．05）。③红斑组病人Th1/Th2、IL－12p35较正常组降低（P均＜0．05）；IL－10R较正常组显著增高IP＜0．05）。④RNP阳性组病人IL－10、IL－12p40较正常组升高，IL－2p35较正常组降低（P均＜0．05）。结论：SLE是一种以Th1细胞下降，Th2细胞相对占优势的免疫介导的自身免疫性疾病，源于诱导向Th1细胞分化的IL－12及其受体养活和细胞因子间失衡所致。     

系统性红斑狼疮患者外周血单个核细胞分泌白细胞介素-10 干扰素-γ水平的研究

目的：通过检测系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）分泌细胞因子白细胞介素－10（IL－10）、干扰素－γ（IFN－γ）水平，探讨了T淋巴细胞亚群与SLE发病关系。方法：采用酶联免疫吸附法（ELISA）测定30例SLE患者和10名健康志愿者PBMC培养上清IL－10和IFN－γ水平。结论：①SLE活动组PBMC自发分泌IL－10水平明显升高，与非活动组、对照组比较差异有显著性（P＜0．001）；非活动组明显高于对照组（P＜0．01）。②PBMC分泌IFN－γ水平三组（SLE活动组、非活动组和对照组）比较差异无显著性（P＞0．05）。结论：IL－10、IFN－γ作为区分CD4T细胞亚群的指标之一，间接反映了Th1、Th2细胞活化状态。本文研究结果显示，SLE患者PBMC分泌IL－10水平明显增高，且增高程度与病情活动性相关，IFN－γ分泌水平无明显变化。提出Th2型细胞因子介导的免疫应答在SLE的发病机制中占主导地位，即“Th2优势应答”。我们认为PBMC分泌IL－10水平对SLE诊断和病情活动性监测均有一定临床意义。寻找有效方法调节SLE患者体内IL－10水平，从而调节Th1/Th2平衡，将为治疗SLE开辟一条新途径。     

系统性红斑狼疮患者血清IL—4和INF—γ水平的测定及其临床意义

目的：通过检测系统红斑狼疮（SLE）患者血清白细胞介素－4（IL－4）、γ－干扰素（INF－γ）的水平，探讨T淋巴细胞亚群与SLE发病的关系。方法：采用酶联免疫吸附法测定SLE患者和健康志愿者血清IL－4和INF－γ水平。结果：（1）SLE活动组血清IL－4水平和IL－4／INF－γ比值明显升高，与非活动组和对照组比较，差异有非常显著性（P＜0．001）；（2）血清INF－γ水平三组（SLE活动组、非活动组和对照组）比较，差异无显著性（P＞0．05）；（3）SLE患者激素治疗后血清IL－4水平明显降低。结论：SLE患者血清IL－4水平和IL－4／INF－γ比值明显升高，且与病情活动性相关，INF－γ水平无明显变化，活动性SLE患者存在Th2细胞优势活化状态，破坏了体内Th1/Th2正常平衡。     

肝炎患者血清IL—2、IFN—γ和IL—10检测的意义

目的：探讨检测IL－2、IFN－γ和IL－10对病毒性肝炎患者的临床意义。方法：利用ELISA法检测97例病毒性肝炎患者血清IL－12、IFN－γ和IL－10水平，动态观察45例接受免疫增强剂治疗的慢性肝炎患者上述细胞因子的变化，结果：急性肝炎患者血清IL－12及IFN－γ水平平均明显升高（P＜0．01）；慢性肝炎、肝硬化患者血清中IL－10明显高于正常对照组（P＜0．01）。免疫增强剂治疗获得完全应答反应的患者治疗期间血清IL－12、IFN－γ水平明显上升（P＜0．01），IL－10水平下降（P＜0．05）。无应答者治疗过程中上述细胞因子无明显变化。结论：Th1型免疫应答对机体清除病毒起关键作用。Th2型免疫应答与感染慢性化及疾病持续发展有关，免疫治疗可使部分Th2型免疫应答占优势的慢性肝炎患者转化为Th1型占优势。     

类风湿关节炎患者白细胞介素-6与皮质醇节律的研究

目的：研究类风湿关节炎（RA）患者血清白细胞介素（IL）－6、皮质醇节律及其临床意义。方法：36例RA患者分别为8：00，12：00，16：00，20：00，0：00，4：00用双抗体夹心酶联免疫吸附试验（ELISA）检测其血清IL－6水平，用放射免疫法（RIA）测定皮质醇。结果：36例RA患者皮质醇分泌有明显节律，但与正常对照组相比，其峰值提前，出现于凌晨4点，血清IL－6水平高于对照组（P＜0．01），也存在昼夜节律，IL－6峰值出现在皮质醇峰值之前，经治疗病情稳定后，RA患者血清IL－6水平恢复或接近正常，IL－6与皮质醇节律紊乱得以纠正，相关性分析显示，RA患者血清IL－6水平与血沉（ESR）（P＜0．01，r=0.66)，C反应蛋白（CRP）（P＜0．01，r＝0.71)皮质醇（P＜0．05，r=0.58)呈正相关，结论：RA患者血清IL－6增高，IL－6与皮质醇存在昼夜节律紊乱，这些变化在RA的发病机制中可能具有重要意义。     

类风湿关节炎患者外周血B淋巴细胞共刺激分子的表达及其意义

目的 初步探讨类风湿关节炎(RA)患者免疫功能紊乱的机制。方法 采用流式细胞仪检测RA患者外周血B淋巴细胞共刺激分子CD80、CD86、CD40的表达并用ELISA检测RA患者血清和关节滑膜液中Th1细胞分泌的细胞因子白细胞介素(IL)-2、干扰素-γ和Th2细胞分泌的细胞因子IL-6、IL-10的水平。结果 RA患者外周血B淋巴细胞CD86表达比正常对照组明显下降(P＜0．01),B淋巴细胞CD40表达比正常对照组明显增多(P＜0．05),而B淋巴细胞CD80表达与正常对照组之间差异无显著性(P＞0．05),同时RA患者血清及滑膜液中IL-2、干扰素-γ的水平比正常对照组明显升高(P＜0．01或P＜0．05),而IL-6、IL-10的水平降低(P＜0．01或P＜0．05)。结论 B淋巴细胞共刺激分子CD86、CD40的异常表达可能与RA患者Th1／Th2细胞分泌的细胞因子失衡密切相关,这将为临床治疗RA提供新的思路。     

过敏性哮喘青春期缓解者外周血IL—4、IL—5活性和IgE的变化

目的：阐明过敏性哮喘青春期解者血清IL－4及IL－5活性和IgE的变化，方法采用ELISA法检测IL－4、IL－5活性和IgE，分别对16例青春期缓解者（A组），26例哮喘发作期（B组）及22例哮喘缓解解患者（C组）和20例正常人（D组）进行比较。结果（1）青春期缓解者-5在性未显著升高，明显低于哮喘发作期患者（P＜0．01）和缓解期患者（P＜0．05），与正常人比较差异无显著性（P＞0．05）。（2）青春期缓解者IL－4较哮喘发作期患者明显降低（P＜0．01），与缓解期患者和正常人比较差异无显著性（P＞0．05）。（3）IgE浓度比较作期明显降低（P＜0．01），与政党人比较差异无显著性（P＞0．05），但还未明显低于哮喘缓解期患者（P＞0．05）。结论过敏性喘喘期解者外周血IL－4、IL－5活性明显降低，IgE有一定程度下降，提示IL－4、IL－5、IgE在支气管哮喘发病机制上起着重要作用。     

心房颤动患者心房组织血管紧张素Ⅱ受体表达的研究

目的 探讨心房颤动（房颤）患者心房组织血管紧张素Ⅱ受体（AT－R）基因转录和蛋白质表达的变化。方法 33例风湿性心脏瓣膜病患者，心脏外科手术时取右心耳组织。通过逆转录－聚合酶链反应和免疫组织化学，测量血管紧张素Ⅱ受体1（AT1－R)的血管紧张素Ⅱ受体2（AT2－R）的mRNA和蛋白的相对表达量。结果 窦性心律患者、阵发性房颤及慢性房颤患者之间的心房组织AT1－R手AT2－R的mRNA水平差别均无显著性（P均＞0．05）；AT1－R和AT2－R在各组患者心房组织中主要表达在心房肌细胞；与窦性心律患者相比，阵发性房颤和慢性房颤患者的心房组织AT1－R的蛋白表达均明显减少（P＜0．05；P＜0．01），而AT2－R的蛋白表达均明显增高（P＜0．01；P＜0．05）。结论 心房在房颤时AT1－R表达下调而AT2－R表达上调，提示血管紧张素系统参与了房颤的心房结构重构。     

系统性红斑狼疮患者血清IFN-γ／IL4分泌模式的探讨

目的观察在系统性红斑狼疮（SLE）免疫紊乱过程中患者血清IFN-γ/IL4分泌模式的变化。方法采用ELISA双抗夹心法检测36例SLE患者和32例健康人血清中IL-4和IFN-γ的水平,并结合补体C3检测结果进行分析。结果SLE病人血清IFN-γ和IL-4水平显著升高（P均〈0．01）,其IFN-γ／IL-4值呈两极化分布特点,以0．76为界,分为高值组（n=19,1．93±1．14）和低值组（n=17,0．53±0．09）（两组间比较,P〈0．01）;与正常对照组比较,低值组该比值显著降低（P〈0．01）,IL-4显著升高（P〈0．01）,高值组该比值和IFN-γ显著升高（P均〈0．01）;SLE患者病情活动期血清补体C3含量显著低于非活动期（P〈0．01）,IL-4、IFN-γ和IFN-γI/L-4在活动期与非活动期患者之间比较无显著性差异。结论SLE患者Th1／Th2细胞因子分泌模式复杂,不同患者可能分别表现为Th1或Th2优势,而与疾病的活动性无关。     

Runx3过表达对慢性乙型肝炎患者Th1、Th2型细胞因子表达的影响

目的：探讨 Runx3过表达对 CHB 患者 Th1、Th2型细胞因子表达水平的影响。方法重组慢病毒载体pGC-FU-Runx3与阴性对照慢病毒载体 pGC-FU 分别转染29例 CHB 患者外周血 CD4＋ T 细胞,收集培养3 d、5 d 和7 d的细胞培养上清液,应用 ELISA 检测 Th1型细胞因子 IFN-γ、IL-2和 Th2型细胞因子 IL-4、IL-10的表达水平。结果与pGC-FU 转染组比较,pGC-FU-Runx3转染组 Th1型细胞因子 IFN-γ的表达水平在3 d（P ＜0．05）、5 d（P ＜0．01）和7 d （P ＜0．01）时均明显升高;IL-2的表达水平在3 d 时差异无统计学意义（P ＞0．05）,但在5 d（P ＜0．05）和7 d（P ＜0．01）时均明显升高。与 pGC-FU 转染组比较,pGC-FU-Runx3转染组 Th2型细胞因子 IL-4的表达水平在3 d 时差异无统计学意义（P ＞0．05）,但在5 d（P ＜0．01）和7 d（P ＜0．05）时均明显降低;IL-10的表达水平在3 d 时差异无统计学意义（P ＞0．05）,但在5 d（P ＜0．05）和7 d（P ＜0．05）时均明显降低。与 pGC-FU 转染组比较,pGC-FU-Runx3转染组 IFN-γ／IL-4比值在3 d（P ＜0．01）、5 d（P ＜0．01）和7 d（P ＜0．01）时均明显增大。结论 Runx3过表达可以促进 CHB 患者 Th1型细胞因子的分泌,抑制 Th2型细胞因子的分泌,使其 Th1／Th2失平衡得到改善。     

糖皮质激素对Th1／Th2平衡的影响

最近10年积累的证据显示,糖皮质激素可抑制抗原提呈细胞和Th1细胞表达自细胞介素（IL）-12、干扰素（IFN）-γ、IFN-α和肿瘤坏死因子（TNF）-α,而上调Th2细胞表达IL-4、IL-10和IL-13。通过以上机制,使用糖皮质激素会选择性抑制Th1介导的细胞免疫,并向Th2介导的体液免疫偏移,而不是对Th1和Th2均产生抑制。在免疫反应和炎症反应过程中,应激系统激活,糖皮质激素水平升高,诱导向Th2偏移,从而使机体免于Th1／促炎细胞因子和激活的巨噬细胞产生的其他产物的损伤。尽管如此,引起糖皮质激素水平较大变化的情况,如急性或慢性应激、剧烈运动、妊娠、产褥期等,均可通过调节Th1／Th2细胞平衡而引起感染和自身免疫、变态反应性疾病或改变其敏感性。     

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro

AIM: To investigate the effects of activated rat hepatic stellate cells(HSCs) on rat Th1/Th2 profile in vitro.METHODS: Growth and survival of activated HSCs and CD4+ T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4+ T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon(IFN)-γ+] and Th2 [interleukin(IL)-4+] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4+ T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs.RESULTS: Co-culture of CD4+ T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions(-1.73% ± 0.71%; P 0.05), whereas the proportion of Th2 cells was not altered; the Th1/Th2 ratio was significantly decreased(-0.44 ± 0.13; P 0.05). In addition, the level of IFN-γ in Th1 cells wasdecreased(-65.71 ± 9.67; P 0.01), whereas the level of IL-4 in Th2 cells was increased(82.79 ± 25.12; P 0.05) by co-culturing, as measured by mean fluorescence intensity by flow cytometry. Apoptosis rates in Th1(12.27% ± 0.99%; P 0.01) and Th2(1.71% ± 0.185%; P 0.01) cells were increased 24 h after co-culturing with activated HSCs; the Th1 cell apoptosis rate was significantly higher than in Th2 cells(P 0.01). Galectin-9 protein expression was significantly decreased in HSCs only 24 h after coculturing(P 0.05) but not after 48 h. Co-culture for 48 h significantly increased the differentiation of Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells(1.85% ± 0.48%; P 0.05).CONCLUSION: Activated rat HSCs lower the Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.     

γδT细胞在肺部铜绿假单胞菌感染的研究现状

γδT细胞是T细胞的一个亚群,存在Th1／Th2免疫模式,主要分布在皮肤、肠道、呼吸道及泌尿生殖道的黏膜和皮下组织,在感染性疾病的免疫应答中发挥着第一道防线的作用。铜绿假单胞菌是临床常见的致病菌,感染所诱发的免疫反应是以Th2型为主,伴有明显的第Ⅲ型超敏反应所导致的器官损害。铜绿假单胞菌感染时γδT细胞明显升高,γδT细胞可能通过分泌不同的细胞因子影响Th1／Th2平衡,进而影响铜绿假单胞菌感染性疾病的发生、发展。     

Toso controls encephalitogenic immune responses by dendritic cells and regulatory T cells

The ability to mount a strong immune response against pathogens is crucial for mammalian survival. However, excessive and uncontrolled immune reactions can lead to autoimmunity. Unraveling how the reactive versus tolerogenic state is controlled might point toward novel therapeutic strategies to treat autoimmune diseases. The surface receptor Toso/Faim3 has been linked to apoptosis, IgM binding, and innate immune responses. In this study, we used Toso-deficient mice to investigate the importance of Toso in tolerance and autoimmunity. We found that Toso^−/− mice do not develop severe experimental autoimmune encephalomyelitis (EAE), a mouse model for the human disease multiple sclerosis. Toso^−/− dendritic cells were less sensitive to Toll-like receptor stimulation and induced significantly lower levels of disease-associated inflammatory T-cell responses. Consistent with this observation, the transfer of Toso^−/− dendritic cells did not induce autoimmune diabetes, indicating their tolerogenic potential. In Toso^−/− mice subjected to EAE induction, we found increased numbers of regulatory T cells and decreased encephalitogenic cellular infiltrates in the brain. Finally, inhibition of Toso activity in vivo at either an early or late stage of EAE induction prevented further disease progression. Taken together, our data identify Toso as a unique regulator of inflammatory autoimmune responses and an attractive target for therapeutic intervention.More than 5% of the populations of Western countries suffer from inflammatory autoimmune diseases (1). In all cases, a hyperactivated immune system is responsible for the initiation of autoimmunity. In the periphery, inflammatory T cells such as IL-17–producing Th (Th17) and IFN-γ–producing Th1 cells are controlled by suppressive regulatory T (Treg) cells (2). Numeric or functional imbalance of these various T-cell populations can result in autoimmunity or immunodeficiency. How the immune system limits self-reactive inflammatory responses in healthy individuals, and how these mechanisms fail in patients, is still under intensive investigation.The transmembrane receptor Toso belongs to the Ig superfamily, and its cytoplasmic domain shows homology to Fas-activated serine/threonine kinase (3). Toso has been implicated in the regulation of CD95 (Fas/Apo1)- and TNF receptor (TNFR)-dependent T-cell apoptosis, and is highly overexpressed in apoptosis-resistant B-cell lymphomas (3–6). Toso also functions as an Fc receptor for IgM, and so may be important for B-cell development (7–10). Recently, Toso expression was detected on granulocytes and monocytes and Toso was linked to the homeostasis and activation of the innate immune system (11–13). However, the precise physiological relevance of Toso’s multifaceted functionality is still unknown.In this study, we investigated the impact of loss of Toso on inflammatory autoimmune responses. Toso-deficient (Toso^−/−) mice were less susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). Disease resistance was dependent on Toso’s function in dendritic cells (DCs). DCs from Toso^−/− mice initiated less intense inflammatory CD4⁺ and CD8⁺ T-cell responses that were associated with reduced immunopathology. Toso^−/− DCs induced more Tregs than controls. Finally, interference with Toso activity in vivo significantly decreased the burden of EAE disease following induction. Our findings indicate that Toso is a crucial mediator of inflammatory autoimmune responses in vivo.     

Evaluation of T cell responses in healing and nonhealing leishmaniasis reveals differences in T helper cell polarization ex vivo and in vitro

Experimental leishmaniasis is widely used to study the effector functions of T helper cell subsets in vivo . Healing and nonhealing Leishmania major infections have been correlated with T helper 1 and T helper 2 responses, respectively. In the present study, we determined T cell effector functions ex vivo , without any further restimulation and compared them to those obtained following antigen-specific restimulation in vitro . Our results show that T helper cell responses are significantly less polarized when determined ex vivo as compared to those measured after restimulation in vitro . Moreover, the differences in CD4⁺ T cell proliferation observed between healer and nonhealer strains of mice differed ex vivo and in vitro . Our results suggest that determination of both ex vivo as well as in vitro T cell responses is crucial to characterize immune responses during experimental leishmaniasis.     

炎症性肠病患者外周血辅助性T细胞1和辅助性T细胞17水平及其临床意义

 目的 探讨炎症性肠病（IBD）患者外周血Th1和Th17细胞水平对IBD发病及活动度的意义。方法 收集2011年5月至2012年7月健康对照者40例和IBD患者81例［其中克罗恩病（CD）39例,溃疡性结肠炎（UC）42例］,采集外周血标本。分离外周血单个核细胞,经PMA及伊屋诺霉素联合刺激、培养后,利用流式细胞仪检测Th1和Th17细胞在外周血CD⁺₄T细胞中的百分比,并结合临床资料分析其临床意义。结果 （1）CD组及UC组Th1细胞百分比［(38.32±16.18)%和(34.23±11.60)%］均明显高于健康对照组［(24.58±10.02)%］（P值均<0.01）,而CD组及UC组的差异无统计学意义;CD及UC缓解期患者的Th1细胞百分比均低于活动期患者［(26.50±9.24)%比(48.46±13.83)%,P<0.01;(30.05±7.41)%比(37.68±13.35)%,P<0.05］。（2）CD组及UC组Th17细胞百分比［(2.51±1.59)%和(4.15±2.75)%］均高于健康对照组［(1.44±0.73)%］（P值均<0.01）,且UC组这一比例高于CD组（P<0.01）;CD及UC活动期患者的Th17细胞百分比明显高于缓解期患者［(3.39±1.56)%比(1.48±0.81)%,(5.77±2.77)%比(2.18±0.59)%,P值均<0.01］。（3）UC组外周血Th17/Th1比值（0.14±0.11）高于CD组（0.08±0.06）和健康对照组（0.07±0.06）,P值均<0.01。结论 IBD患者外周血中Th1、Th17细胞占CD⁺₄T细胞比例较健康人群明显升高,且与IBD活动度密切相关。Th1和Th17细胞在IBD发病中可能具有重要作用。     

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon- after purified protein derivative stimulation (P<0.02). More cells secreting interferon- were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P<0.03). The number of cells secreting interferon- in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P<0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P=0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.This study was supported by grants from The Swedish Medical Research Council (7129), foundations of the Karolinska Institute, the Nanna Svartz foundation, the Swedish Society of Medicine, and the Ruth and Richard Juhlin foundation.     

Filaria/Wolbachia activation of dendritic cells and development of Th1-associated responses is dependent on Toll-like receptor 2 in a mouse model of ocular onchocerciasis (river blindness)

Toll-like receptors (TLRs) regulate dendritic cell function and activate signals that mediate the nature of the adaptive immune response. The current study examined the role of TLRs in dendritic cell activation and in regulating T cell and antibody responses to antigens from the filarial parasites Onchocerca volvulus and Brugia malayi, which cause river blindness and lymphatic filariasis, respectively. Bone-marrow-derived CD11c(+) cells from C57BL/6 and TLR4(-/-) mice produced high levels of IL-6 and RANTES, and showed elevated surface CD40 expression, whereas CD11c(+) cells from myeloid differentiation factor 88(-/-) (MyD88(-/-)), TLR2(-/-) and TLR2/4(-/-) mice were not activated. Similarly, IFN-gamma production by splenocytes from immunized TLR2(-/-) mice was significantly impaired compared with splenocytes from C57BL/6 and TLR4(-/-) mice. In contrast, there was no difference among these strains in Th2-associated responses including IL-5 production by splenocytes from immunized animals, serum IgE and IgG(1), or eosinophil infiltration into the corneal stroma. Neutrophil recruitment to the cornea and CXC chemokine production was inhibited in immunized TLR2(-/-) mice compared with C57BL/6 and TLR4(-/-) mice. Taken together, these findings demonstrate an essential role for TLR2 in filaria-induced dendritic cell activation, IFN-gamma production and neutrophil migration to the cornea, but does not affect filaria-induced Th2-associated responses.     

类风湿关节炎患者外周血疱疹病毒DNA的检测及其Th亚群激活状况研究

目的　研究类风湿关节炎 (RA)患者疱疹病毒感染情况以及Th亚群的激活状况。方法　通用引物PCR扩增 32份RA患者和 36份健康对照者全血和血清标本EB病毒 (EBV)、巨细胞病毒(CMV)、疱疹病毒 (HSV) 1、HSV 2DNA ,并用限制性内切核酸酶SmaⅠ、BamHⅠ进行酶切鉴定 ;酶联免疫吸附测定 (ELISA)法检测 36例RA患者和 2 5名健康对照血清干扰素 (IFN) γ、白细胞介素 14(IL 4)水平 ,并与健康对照组进行比较。结果　①RA患者全血与血清标本疱疹病毒DNA检出率分别为6 2 %和 3 1% ,健康对照组分别为 0和 2 8%。②RA患者血清IFN γ水平 (2 1± 33)pg/ml及IFN γ/IL 4比值 2 5± 2 0显著高于健康对照 (10 1± 2 6 ) pg/ml和 17± 8,P均 <0 0 5。IL 4在两组间的差异无显著性。③IFN γ水平及IFN γ/IL 4比值与RA病情严重程度显著相关。结论　①HSV、EBV、CMV等疱疹病毒DNA检出率与RA发病无相关性。②RA患者体内存在Th1(主要分泌IFN γ)与Th2 (主要分泌IL 4)激活比例失衡的现象。主要分泌致炎性细胞因子的Th1细胞活性增高而主要分泌抗炎性细胞因子的Th2细胞活性相对不足 ,这可能与RA患者慢性持续性关节炎症有关。