Current status of hepatitis C virus infection in Korea

Chronic liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC), has been a major cause of mortality in Korea. The prevalence rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in the general population of Korea are approximately 1 and 5%, respectively. The most common genotypes of HCV in Korea are 1b and 2a. The sustained virological response rates after antiviral therapies, including combined interferon-alpha and ribavirin, have been reported to be 38-59%. The annual incidence of HCC among HCV-related liver cirrhosis has been estimated at 5%, and approximately 12% of HCC is attributable to HCV and 68% to HBV in Korea. The mean age of patients with HCV-related HCC at the time of diagnosis was consistently 10 years older than that of patients with HBV-related HCC. Moreover, HCV-related HCC was accompanied by more advanced liver cirrhosis than HBV-related HCC. Coinfection with HBV seemed to increase the risk of developing HCC in chronic HCV infection. After the successful program of hepatitis B vaccination, HCV infection is now emerging as an important etiology of chronic liver disease in Korea, which warrants more detailed and large-scale studies.     

钥孔戚血蓝蛋白诱导Balb/C小鼠脾细胞Th1/Th2失衡

背景:建立具有一定特征的、稳定的、可重复性强的Th1/Th2失衡动物模型是研究Th1/Th2失衡机制的重要基础.目的:分析钥孔戚血蓝蛋白诱导Balb/C小鼠脾细胞Th1/Th2失衡的特点.设计:随机对照探索性实验.单位:河北医科大学基础医学院河北省法医学实验室.材料:实验于2005-09/2007-02在河北医科大学基础医学院河北省法医学实验室完成.实验选用Balb/c小鼠,对动物处置方法符合动物伦理学要求.方法:①以钥孔戚血蓝蛋白 完全弗氏佐剂免疫Balb/C小鼠,分离脾细胞,细胞因子分泌高峰点测定实验分为3组,分别为钥孔戚血蓝蛋白6.25,12.5,25 mg/kg组:不同免疫剂量和免疫次数实验分为7组.分别为钥孔戚血蓝蛋白6.25,12.5,25 me/kg组,6.25,12.5,25 mg/kg二次免疫组及对照组.主要观察指标:以酶联免疫吸附法检测小鼠脾细胞培养上清中Th1型细胞因子γ-干扰素、白细胞介素2、白细胞介素12 p40及Th2型细胞因子白细胞介素4、白细胞介素5的分泌量及血清中Th1型抗体IgG2a和Th2型抗体IgG1水平.结果:①钥孔戚血蓝蛋白免疫使小鼠出现脾肿大,脾细胞计数增高.②体外同种抗原再刺激使免疫小鼠脾细胞培养上清中4种细胞因子浓度增高,其中白细胞介素2分泌量于24h即明显增高,48 h达高峰:白细胞介素4、γ-干扰素和白细胞介素5在24 h轻度增高,以后逐渐上升,96 h达高峰.各时间点培养上清中白细胞介素12p40含量均较低,与对照组无明显差异.③不同剂量单次或二次免疫均可致4种细胞因子不同程度增高,白细胞介素4/γ-干扰素比值增高,其中12.5 mg/kg钥孔戚血蓝蛋白二次免疫组细胞因子分泌量明显高于其他各组(P＜0.01).④钥孔戚血蓝蛋白免疫小鼠血清IgG1,IgG2a水平发生不同程度增高,其中IgG1增高更为明显.结论:钥孔戚血蓝蛋白加完全弗氏佐剂可诱导Balb/C小鼠脾细胞发生Th2型优势反应.     

束缚应激条件下S180荷瘤小鼠Th1/Th2细胞因子失衡与肿瘤的生长

背景束缚是研究心理应激的可靠方法.束缚应激可以通过下丘脑-垂体-肾上腺轴抑制T细胞免疫.目的观察束缚应激状态下小鼠体内Thl/Th2平衡的改变以及荷瘤小鼠肿瘤生长情况,并试图发现心理应激对肿瘤细胞生长的影响.设计以实验动物为研究对象的对照研究.单位北京中医药大学基础医学院微生物学与免疫学教研室.材料实验在北京中医药大学基础医学院免疫学实验室开展.选择鼠龄6～8周的昆明种小鼠为实验对象.购进后适应性饲养3 d,称质量,并按体质量顺序编号,剔除体质量最大和最小的个体,再随机分入4个实验组中.分组后每组有小鼠16只(雌雄各8只),体质量18～20 g.方法取腹腔传代第7天的肿瘤细胞S180,用生理盐水洗涤后,用RPMI1640细胞培养基调细胞密度至1×1010L-1,在单纯肿瘤组和肿瘤束缚组小鼠右腋皮下注射0.2 mL/只.同时在正常对照组和单纯束缚组相同部位注射生理盐水0.2 mL/只,接种后将单纯束缚组和肿瘤束缚组小鼠用特制小管限制活动,8 h/d.10 d后处死小鼠,剥取肿瘤和胸腺并分别称其质量,计算胸腺指数,分别采用四甲基偶氮唑盐比色法和丝裂原激活淋巴母细胞法检测脾T细胞增殖及产生Thl型细胞因子白细胞介素2、干扰素γ的能力,并取血清用酶联免疫吸附法检测Th2型细胞因子白细胞介素4、白细胞介素10的含量.主要观察指标主要结局束缚应激对T细胞产生Thl型细胞因子白细胞介素2、干扰素γ的能力和Th2型细胞因子白细胞介素4和白细胞介素10的影响,以及对荷瘤小鼠肿瘤生长的促进作用.次要结局束缚应激对小鼠T细胞增殖能力的抑制作用和对胸腺指数的影响.结果束缚应激可明显增加荷瘤小鼠的瘤质量,降低小鼠胸腺指数和脾T细胞的增殖能力,降低荷瘤小鼠脾细胞产生白细胞介素2和干扰素γ的能力,并可使小鼠血清白细胞介素4和白细胞介素l0的含量明显增加.结论束缚应激可显著抑制荷瘤小鼠的细胞免疫功能,使产生Thl型细胞因子的功能减弱,Th2型细胞因子的含量增加,导致Thl/Th2细胞的平衡进一步向Th2细胞漂移.这可能是其促进肿瘤生长的重要机制.     

Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma

T helper type 1 (Th1)-type CD4(+) antitumor T cell help appears critical to the induction and maintenance of antitumor cytotoxic T lymphocyte (CTL) responses in vivo. In contrast, Th2- or Th3/Tr-type CD4(+) T cell responses may subvert Th1-type cell-mediated immunity, providing a microenvironment conducive to disease progression. We have recently identified helper T cell epitopes derived from the MAGE-6 gene product; a tumor-associated antigen expressed by most melanomas and renal cell carcinomas. In this study, we have assessed whether peripheral blood CD4(+) T cells from human histocompatibility leukocyte antigens (HLA)-DRbeta1*0401(+) patients are Th1- or Th2-biased to MAGE-6 epitopes using interferon (IFN)-gamma and interleukin (IL)-5 enzyme-linked immunospot assays, respectively. Strikingly, the vast majority of patients with active disease were highly-skewed toward Th2-type responses against MAGE-6-derived epitopes, regardless of their stage (stage I versus IV) of disease, but retained Th1-type responses against Epstein-Barr virus- or influenza-derived epitopes. In marked contrast, normal donors and cancer patients with no current evidence of disease tended to exhibit either mixed Th1/Th2 or strongly Th1-polarized responses to MAGE-6 peptides, respectively. CD4(+) T cell secretion of IL-10 and transforming growth factor (TGF)-beta1 against MAGE-6 peptides was not observed, suggesting that specific Th3/Tr-type CD4(+) subsets were not common events in these patients. Our data suggest that immunotherapeutic approaches will likely have to overcome or complement systemic Th2-dominated, tumor-reactive CD4(+) T cell responses to provide optimal clinical benefit.     

乳腺癌手术前后辅助性T淋巴细胞1、2型细胞因子的表达及意义

目的 观察手术前后乳腺癌患者体内辅助性T淋巴细胞(helper Tlymphocyte,Th)1、2型细胞因子的表达及意义.方法 2009年11月-2010年12月,采用酶联免疫吸附试验检测40例乳腺癌患者(乳腺癌组)手术前、后和15例健康妇女(正常对照组)外周血单个核细胞培养上清液中Thl型细胞因子[白细胞介素(in...     

系统性红斑狼疮患者血清催乳素水平与Th1/Th2细胞因子平衡研究

目的 探讨系统性红斑狼疮(SLE)患者外周血催乳素(PRL)水平、Th1/Th2细胞因子分泌模式与SLE患者病情活动的关系.方法 检测40例SLE患者(SLE组)血清PRL IFN-γ、IL-4水平,分析二者与SLE病情活动的关系并与20例健康献血者(对照组)比较.结果 ①SLE组较正常对照组血清PRL[(21.58±4.29)ng/ml与(11.87±2.57)ng/ml,P<0.01)]、IL-4[(26.79±5.08)ng/L与(10.71±1.35)ng/L,P<0.01)]高,而IFN-γ[(11.47±3.36)ng/L与(18.36±2.61)ng/L,P<0.01)]、IFN-γ/IL-4(0.76±0.29与2.30±0.15,P<0.01)较正常对照组低.②SLE病情活动组PRL[(28.07±6.36)ng/ml与(14.61±2.14)ng/ml,P<0.01)]、IL-4[(38.52±8.44)ng/L与(14.15±1.63)ng/L,P<0.01)]高于病情稳定组,而IFN-γ[(6.98±2.72)ng/L与(16.24±2.57)ng/L,P<0.01)]、IFN-γ/IL-4(0.35±0.14与1.24±0.29,P<0.01)水平低于病情稳定组.③SEE活动期组10例患者治疗好转后较治疗前PRL[(39.41±11.65)ng/ml与(14.49±8.65)ng/ml,P<0.01)]、IL-4[(45.12±10.44)ng/L与(17.53±5.42)ng/L,P<0.01)]下降,IFN-γ[(6.31±2.59)ng/L与(16.89±4.43)ng/L,P<0.01)]、IFN-γ/IL-4(0.16±0.11与1.16±0.27,P<0.01)回升.结论 SLE患者存在高PRL血症及Th2细胞因子优势,高PRL血症和Th1/Th2比值失衡程度与病情活动呈消长关系.     

慢性自发性荨麻疹患者血清维生素D、脱氢表雄酮硫酸酯水平与Th1/Th2细胞因子及免疫球蛋白的关系分析

目的探讨不同程度慢性自发性荨麻疹(CSU)患者血清维生素D、脱氢表雄酮硫酸酯(DHEA-S)水平与辅助性T(Th)1/Th2细胞因子、免疫球蛋白的关系及临床意义。方法选取北京京城皮肤医院2016年1月至2017年12月收治的137例CSU患者作为观察组,依据CSU病情分级将观察组分为轻度组(59例)、中度组(41例)、重度组(37例),选取同期该院体检健康者70例作为对照组。比较观察组与对照组、不同CSU病情分级患者血清25-羟基维生素D[25(OH)D]、DHEA-S、Th1/Th2细胞因子、免疫球蛋白水平。结果与对照组比较,观察组血清25(OH)D、DHEA-S、白细胞介素(IL)-2、干扰素(IFN)-γ水平较低,血清IL-4、免疫球蛋白(Ig)E、IgG水平较高(P<0.05)。轻、中、重度组血清25(OH)D、IL-2、IL-4、IFN-γ水平整体比较,差异无统计学意义(P>0.05);病情越重,血清DHEA-S水平越低,IgE、IgG水平越高(P<0.05)。CSU患者血清25(OH)D与IL-2水平呈正相关,与IL-4、IFN-γ水平呈负相关(P<0.05);CSU患者血清DHEA-S与IL-2、IFN-γ水平呈正相关,与IL-4、IgE水平呈负相关(P<0.05)。结论CSU患者血清维生素D水平的降低可能与Th1/Th2细胞失衡相关,血清DHEA-S水平的降低则可能与Th1/Th2细胞失衡及病情的进展相关,也可能与IgE介导的Ⅰ型变态反应相关。     

A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12

Leishmania braziliensis causes cutaneous and mucosal leishmaniasis in humans. Most patients with cutaneous leishmaniasis heal spontaneously and may therefore have developed protective immunity. There appears to be a mixed cytokine profile associated with active cutaneous or mucosal disease, and a dominant T helper (Th)1-type response associated with healing. Leishmanial antigens that elicit these potent proliferative and cytokine responses from peripheral blood mononuclear cells (PBMC) are now being identified. Herein, we report on the cloning and expression of a L. braziliensis gene homologous to the eukaryotic ribosomal protein eIF4A (LeIF) and patient PBMC responses to rLeIF. Patients with mucosal and self-healing cutaneous disease had significantly higher proliferative responses than those with cutaneous lesions. Whereas the parasite lysate stimulated patient PBMC to produce a mixed Th1/Th2-type cytokine profile, LeIF stimulated the production of interferon gamma (IFN-gamma), interleukin 2 (IL-2), and tumor necrosis factor alpha but not IL-4 or IL-10. Recombinant LeIF (rLeIF) downregulated both IL-10 mRNA in the "resting" PBMC of leishmaniasis patients and LPS-induced IL-10 production by patient PBMC. rLeIF also stimulated the production of IL-12 in cultured PBMC from both patients and uninfected individuals. The production of IFN-gamma by patient PBMC stimulated with either rLeIF or parasite lysate was IL-12 dependent, whereas anti-IFN-gamma monoclonal antibody only partially blocked the LeIF-induced production of IL-12. In vitro production of both IFN-gamma and IL-12 was abrogated by exogenous human recombinant IL-10. Therefore, we have identified a recombinant leishmanial antigen that elicits IL-12 production and Th1-type responses in patients as well as IL-12 production in normal human PBMC.     

Th1/Th2 balance in systemic inflammatory response syndrome (SIRS)

The activation of a pro-inflammatory cascade after infection, major surgery, burn or trauma appears to be important in the development of subsequent immune dysfunction, susceptibility to sepsis and multiple organ failure. It is well known that T-cell plays a critical role in the systemic response to infection. Distinct patterns of cytokines are produced by two different types of T-helper cells (Th). Th1 lymphocytes produce IFN-gamma and IL-2, favoring cell mediated immunity; Th2 cells secrete IL-4, IL-5, IL-10, IL-13, favoring humoral immunity. Cytokines produced in systemic inflammatory response syndrome (SIRS) may effect Th subset predominance and subsequent immune responses. We measured Thl/Th2 balance in patients with severe sepsis, SIRS patients with non sepsis, and healthy subjects by flow cytometry. In patients with severe sepsis, Th2 antibody mediated (humoral) immune responses predominate. We believe that severe sepsis clearly induce polarization of T-helper lymphocyte activity with a clear shift in Th2 direction. This type of response may lead immunosuppression. Modulation of Th cell subset predominance may present a novel therapeutic option in the treatment of severe sepsis.     

Polarized type-1 dendritic cells (DC1) producing high levels of IL-12 family members rescue patient TH1-type antimelanoma CD4+ T cell responses in vitro

Deficiencies in TH1-type immunity in patients with cancer may facilitate tumor progression and limit the effectiveness of current immunotherapy approaches. We hypothesized that Type-1 polarized dendritic cells (DC1) might be able to recondition patient antitumor CD4+ T cell responses toward the TH1-type in vitro. Although DC1 have been previously demonstrated to prime TH1 responses from naive CD4+ T cells, their impact on antigen-experienced TH responses remains unknown. We confirmed our own earlier observations that patient CD4+ T cell reactivity against melanoma-associated antigens (MAA) was weaker and less Type-1-polarized than their corresponding antiviral responses. Stimulation of patient CD4 T cells with peptide-pulsed DC1 (producing multiple IL-12 family member cytokines, including IL-12p70, IL-23, and IL-27) promoted robust TH1-type, epitope-specific T cell responses. Addition of exogenous IL-12 family member cytokines alone, or in combination, to nonpolarized DC was insufficient to equate to the benefits associated with DC1-based stimulation; however, IL-27 and IL-12p70 blockade neutralized the ability of DC1 cells to enhance TH1-type antitumor immunity in vitro. Notably, DC1-based stimulation seemed capable of "revitalizing" defective TH1-type responses within the CD45RO+ subset of antigen-experienced CD4+ T cells in melanoma patients. In addition to promoting elevated levels of IFN-gamma from responder CD4+ T cells, DC1-based stimulation also led to increased levels of IL-12Rbeta2 and t-bet expression by TH cells. These results suggest that preexisting CD4+ T cell immunity to cancer is not relegated to Type-1 insufficiency and may be corrected via the application of DC1-based vaccination protocols.     

Innate immune response in Th1- and Th2-dominant mouse strains

C57BL/6 and BALB/c mice are prototypical Th1- and Th2-type mouse strains, respectively. In the present study, we attempted to characterize the innate immune response of macrophages from these mouse strains. Macrophages from C57BL/6 mice produced higher levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12 than those from BALB/c mice after stimulation with macrophage-activating lipopeptide-2 (MALP-2, a synthetic TLR-2 ligand) or lipopolysaccharide (LPS, a TLR-4 ligand). The augmented IL-12 production by C57BL/6 macrophages increased interferon-gamma and, in contrast, decreased IL-13 production by CD4+ T cells. On stimulation with MALP-2 or LPS, C57BL/6 macrophages produced lysosomal enzyme and nitric oxide, effector molecules for bacterial killing, whereas BALB/c macrophages did not. Bactericidal activity of BALB/c macrophages was impaired relative to C57BL/6 macrophages when cells were infected with live bacteria in vitro. In a murine model of septic peritonitis induced by cecal ligation and puncture (CLP), BALB/c mice failed to facilitate bacterial clearance relative to C57BL/6 mice despite an augmented peritoneal leukocyte infiltration that was associated with increased peritoneal levels of cytokines/chemokines. BALB/c mice exhibited increased plasma and hepatic levels of cytokines/chemokines, resulting in an exaggerated systemic inflammation as determined by acute-phase proteins. Finally, BALB/c mice were vulnerable to CLP-induced lethality relative to C57BL/6 mice. Altogether, innate immune response of macrophages is different between these mouse strains, which may affect the development of Th1 and Th2 adaptive immunity in these strains. Reduced systemic inflammatory response in C57BL/6 mice that may result from an eminent local response appears to be beneficial during sepsis.     

Survival rates of early-stage HCV-related liver cirrhosis patients without hepatocellular carcinoma are decreased by alcohol

Although alcohol abuse is the most common cause of liver cirrhosis in the United States, the enhancing effects of alcohol on the long-term prognosis of hepatitis C virus (HCV) related liver cirrhosis has not been clarified. To investigate how alcohol abuse influences the prognosis of hepatitis virus related liver cirrhosis, we studied 716 Japanese patients. Cumulative survival and hepatocellular carcinoma (HCC) development rates were analyzed in alcohol abusive, cirrhotic patients with or without hepatitis virus infection. Patients who abused alcohol were younger (p<0.0001) than HCV infected, non-abusive patients. The overall survival rate among patients with alcoholic cirrhosis (Al group), HCV related cirrhosis (HCV group), and HCV infected + alcoholic cirrhosis (HCV + Al group), showed no significant differences, although the 10-year cumulative survival rate of Al group was the highest of the three groups. The HCC development rate of Al group was the lowest. In addition, alcohol abuse decreased the survival rates of HCV group in the early stage with no HCC (p = 0.0028). In conclusion, alcohol abuse might affect the progression of liver damage in HCV infected patients with liver cirrhosis in the early stage, although the influence of alcohol abuse on the long term prognosis seems to be rather small.     

HCV抗原诱导Th1/Th2细胞增殖活性分析及其在丙型肝炎诊断中的应用

目的　通过检测Th1 Th2特征性细胞因子 ,分析Th1 Th2细胞增殖活性 ,探讨其在丙型肝炎慢性化进程中的免疫学作用 ,研究HCV感染者肝病慢性化的免疫学因素。方法　首先用淋巴细胞分离液分离丙肝病毒感染者的PB MC ,纯化其CD+4T细胞 ,然后用HCV混合Ag刺激培养CD+4T细胞 ,最后用ELISA法检测IL 2、IL 4的含量 ,分析Th1和Th2细胞增殖活性。结果　本课题研究病例共包括 2 3例急性肝炎病例 (其中 7例呈自限性病程 ,16例转变为慢性肝炎 )和 2 0例慢性肝炎病例 ,以上病例CD+4T细胞经HCV混合抗原刺激培养后 ,其中 7例急性自限性病例表现为Th1样反应 (IL 2分泌增加 ) ,与 16例急性转慢性病例比较有显著性差异 (t =2 1.76、P <0 .0 1) ;7例自限性病例在HCVAg刺激前后Th1样反应有显著性差异 (t =18.15、P <0 .0 1)。 16例急性转慢性病例表现为Th2样反应 (IL 4分泌增加 ) ,与 7例自限性病例比较有显著性差异 (t =7.75、P <0 .0 1) ;16例急性转为慢性病例在HCVAg刺激前后Th2样反应有显著性差异 (t=4 .0 8、P<0 .0 1)。 2 0例慢性化病例主要为Th2样反应 ,其与急转慢性病例无显著性差异 (t=1.0 1、P >0 .0 5 )。结论　HCVAg能够特异性地刺激Th前体细胞向Th1或Th2细胞分化 ;Th1样应答与疾病的好转有关 ,Th2样应答与慢性化有     

Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni

In the mouse, infection with Schistosoma mansoni results in an egg-producing infection and associated disease, whereas vaccination with attenuated larval stages produces a substantial and specific immunity in the absence of egg-induced pathology. Preliminary data showing enhanced interleukin-5 (IL-5) production by T cells from infected mice and interferon gamma (IFN-gamma) synthesis by cells from vaccinated animals (7), suggested differential CD4+ subset stimulation by the different parasite stimuli. To confirm this hypothesis, lymphocytes from vaccinated or infected animals were compared for their ability to produce IFN-gamma and IL-2 (secreted by Th1 cells) as compared with IL-4 and IL-5 (characteristic Th2 cytokines). After stimulation with specific antigen or mitogen, T cells from vaccinated mice or prepatently infected animals responded primarily with Th1 lymphokines, whereas lymphocytes from patently infected mice instead produced Th2 cytokines. The Th2 response in infected animals was shown to be induced by schistosome eggs and directed largely against egg antigens, whereas the Th1 reactivity in vaccinated mice was triggered primarily by larval antigens. Interestingly, Th1 responses in mice carrying egg-producing infections were found to be profoundly downregulated. Moreover, the injection of eggs into vaccinated mice resulted in a reduction of antigen and mitogen-stimulated Th1 function accompanied by a coincident expression of Th2 responses. Together, the data suggest that coincident with the induction of Th2 responses, murine schistosome infection results in an inhibition of potentially protective Th1 function. This previously unrecognized downregulation of Th1 cytokine production may be an important immunological consequence of helminth infection related to host adaptation.     

Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice.

CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to tape-stripped mouse skin by evaluating the production of cytokines and Ig isotypes. Confocal laser scanning microscopy revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Co-administration of CpG-ODN and OVA to the disrupted skin elicited an antigen-specific Th1-predominant immune response and enhanced the production of Th1-type cytokines, IL-12 and IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. Cytokine production was supported by the expression of mRNA in the draining lymph node. In terms of antigen-specific antibody production, the level of IgG2a which is regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed. Furthermore, administration of CpG-ODN via the skin drastically attenuated the production of IgE in mice undergoing IgE-type immune response. Administration of CpG-ODN through the skin may shift the immune response from Th2 to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases like AD, which is characterized by Th2-dominated inflammation.     

Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice

Protective immunity against pathogens such as Leishmania major is mediated by interleukin (IL)-12-dependent Th1-immunity. We have shown previously that skin-dendritic cells (DCs) from both resistant C57BL/6 and susceptible BALB/c mice release IL-12 when infected with L. major, and infected BALB/c DCs effectively vaccinate against leishmaniasis. To determine if cytokines other than IL-12 might influence disease outcome, we surveyed DCs from both strains for production of a variety of cytokines. Skin-DCs produced significantly less IL-1alpha in response to lipopolysaccharide/interferon gamma or L. major when expanded from BALB/c as compared with C57BL/6 mice. In addition, IL-1alpha mRNA accumulation in lymph nodes of L. major-infected BALB/c mice was approximately 3-fold lower than that in C57BL/6 mice. Local injections of IL-1alpha during the first 3 d after infection led to dramatic, persistent reductions in lesion sizes. In L. major-infected BALB/c mice, IL-1alpha administration resulted in increased Th1- and strikingly decreased Th2-cytokine production. IL-1alpha and IL-12 treatments were similarly effective, and IL-1alpha efficacy was strictly IL-12 dependent. These data indicate that transient local administration of IL-1alpha acts in conjunction with IL-12 to influence Th-development in cutaneous leishmaniasis and prevents disease progression in susceptible BALB/c mice, perhaps by enhancing DC-induced Th1-education. Differential production of IL-1 by C57BL/6 and BALB/c mice may provide a partial explanation for the disparate outcomes of infection in these mouse strains.     

食管鳞状细胞癌患者血清T辅助细胞类细胞因子的表达及其临床意义

目的 探讨食管癌患者血清T辅助细胞(Th1、Th2)类细胞因子的表达及其临床意义.方法 采用双抗体酶联免疫吸附法(ELISA)检测45例食管鳞状细胞癌患者及30名健康体检者外周血Th1[干扰素(INF)-γ、白细胞介素(IL)-2]、Th2类(IL-4)细胞因子的含量.结果 食管癌患者Th1类细胞因子INF-γ、IL-2表达含量较健康对照组降低[(11.51±2.15)、(16.31±2.27)ng/L,t=18.24,P＜0.01);(10.20±2.10)、(16.92±2.41)ng/L,t=15.31,P＜0.05];Th2类细胞因子(IL-4)较健康对照组升高[(5.30 -0.11)、(2.23±0.29)ng/L,t=5.79,P＜0.05],且其表达趋势与肿瘤的TNM分期有关.结论 食管癌患者体内存在Th1/Th2漂移现象.该现象可能与肿瘤细胞发生免疫逃逸有关.

Abstract：

Objective To study the expression of Th1 and Th2 types cytokines in patients with esophageal squamous cell carcinoma and the clinical significance. Methods The expressions of Th1 ( INF-γ、IL-2) and Th2 (IL-4) types cytokines in cultured peripheral blood mononuclear cells (PBMC) from 30 healthy controls and 45 esophageal squamous cell carcinoma patients were determined by Enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, the expressions of Th1 type cytokines, IL-2 and INF-γwere significantly lower in the cultured PBMCs from the cancer patients (tINF-γ= 18. 24 ,tIL-2 = 15.31 ,Ps ＜0. 01 ) ,while the expression of Th2 type cytokines,IL-4 was significantly higher in the cultured PBMCs from the cancer patients ( tIL-4 = 5.79, P ＜ 0. 05 ). The expression changes of the cytokines showed a correlation with TNM (tumou-node-metastasis) stage of the tumor. Conclusion The Th1/Th2 shift existed in patients with esophageal squamous cell carcinoma and it might be one of the underline mechanisms of tumor immune escape.     

阻塞性睡眠呼吸暂停低通气综合症患者外周血Th1/Th2细胞因子表达水平的研究

目的:检测阻塞性睡眠呼吸暂停低通气综合症(OSAHS)患者外周血CD4+T淋巴细胞分泌的细胞因子水平,探讨患者Th1/Th2相关细胞因子的平衡及其临床意义.方法:47例OSAHS患者按照呼吸暂停低通气指数(AHI)水平分为轻度组(n＝16),中度组(n＝17),重度组(n＝14),18例健康人作为对照组,分别测定各组外周血中Thl细胞因子:干扰素γ (IFN-γ)、白细胞介素2 (IL-2)和肿瘤坏死因子β (TNF-β);Th2的细胞因子:IL-4、IL-10和IL-12的含量.结果:OSAHS各组Thl型细胞因子中IFN-γ高于对照组,随着病情的进展有逐渐升高趋势,但仅在重度组与中度组、轻度组、健康组比较时P均＜0.05,其余Th1/Th2细胞因子在进行两两比较时各组间均无明显差异.OSAHS患者IFN-γ与AHI呈正相关,而Th2细胞因子与AHI无相关关系.结论:OSAHS患者Thl/Th2平衡失调,向Thl方向漂移,Th1细胞表型处于优势状态,且与OSAHS的严重程度相关.     

Changes in the balance between Treg and Th17 cells in patients with chronic hepatitis B

The purpose of this study was to explore the role of Treg cells, Th17 cells and cytokines associated with Treg/Th17 differentiation in the occurrence, development and outcome of chronic hepatitis B (CHB). To do so, we detected populations of Treg and Th17 cells and their associated cytokines in the peripheral blood of CHB patients. The populations of Treg cells (CD4⁺CD25^highCD127^low T cells) and Th17 cells (CD3⁺CD8^-IL-17⁺ T cells) were analyzed in 46 patients with low to moderate chronic hepatitis B (CHB-LM), 24 patients with severe chronic hepatitis B (CHB-S) and 20 healthy controls (HC) using flow cytometry. The levels of cytokines associated with Treg/Th17 differentiation, including IL-10, TGF-β1, IL-17 and IL-23, were measured by enzyme-linked immunosorbent assay (ELISA). Our study showed that the imbalance of Treg and Th17 cells might play an important role in the occurrence, development and outcome of CHB.