T-bet重组腺病毒对哮喘小鼠Thl/Th2免疫平衡的调节

目的探讨静脉应用T-bet重组腺病毒（AdT-bet）对哮喘模型小鼠过敏性气道炎症及Th1／Th2免疫失衡的影响。方法36只C57BL/6小鼠随机分为AdT-bet治疗组（A组）、模型对照组（B组）、正常组（C组）。以卵蛋白（OVA）、氢氧化铝免疫建立哮喘模型，A组激发前尾静脉注射100μL的AdT-bet（1×10^8 PFU/μL），各组激发后肺泡灌洗分析细胞组份，分离肺淋巴细胞测定细胞因子分泌水平，以流式细胞仪检测CD3^＋、CD4^＋ T细胞比例及表达IFNγ和IL-4的比例，比较各组肺组织学改变。结果静脉应用AdT-bet组与对照组相比：①可明显抑制抗原激发后气道内嗜酸性粒细胞的浸润（P〈0．01）；②明显抑制肺淋巴细胞产生IL-4、IL-5，增加了IFNγ的产生；③肺脏淋巴细胞CD4^＋ IFNγ百分比及IFNγ^＋/IL-4^＋明显升高（P〈0．01），而CD4^＋ IL-4^＋百分比则明显下降；④明显抑制哮喘鼠气道内及肺泡内的过敏性炎症反应。结论激发前静脉用AdT-bet对哮喘小鼠过敏性气道炎症有明显的防治作用，其机制可能与表达的T-bet上调Th1／Th2比值，从而调整了免疫平衡有关。     

Immunobiology of lnterleukin-12

Interleukin-12 (IL12) is a heterodimeric cytokine which is produced by phagocytic cells and antigen-presenting cells within a few hours of infection, particularly in the case of bacteria and intracellular parasites, and acts as a proinflammatory cytokine, activating natural killer (NK) cells, and, through its ability to induce interferon-γ (IFNγ) production, enhancing the phagocytic and bacteriocidal activity of phagocytic cells and their ability to release proinflammatory cytokines, including IL12 itself. Furthermore, IL12 produced during the early phases of infection and inflammation, sets the stage for the ensuing antigen-specific immune response, favoring differentiation and function of T helper type 1 (Th1) T cells while inhibiting the differentiation of Th2 T cells. Thus, IL12, in addition to being a potent proinflammatory cytokine, is a key immunoregulator molecule in Th1 responses.     

甘露聚糖结合凝集素缺损与自身免疫性疾病

甘露聚糖结合凝集素(MBL)系胶原凝集素家族成员,是天然免疫系统中的重要分子。血清MBL浓度受其结构基因第一外显子几个点突变的影响和启动子区多态性的调控。MBL基因突变使其血清浓度降低,除导致调理吞噬缺损外,还与自身免疫性疾病如系统性红斑狼疮、类风湿性关节炎、干燥综合征、皮肌炎、克隆病、动脉炎等有关。     

CD2-mediated signaling in T cells lacking the ζ-chain-specific immune receptor tyrosine-based activation (ITAM) motif

T lymphocytes can be activated via the T cell receptor (TCR) or by triggering through a number of other surface structures, including the CD2 co-receptor molecule. Signaling through the CD2 molecule was shown previously to be dependent on the TCR-associated ζ-chain. Here, we show that CD2-induced activation also functions in T cells which express ζ-chains lacking a functional immune-receptor tyrosine-based activation motif (ITAM). TCR-positive T cells that express only the transmembrane part of the ζ-chain protein and thus lack a functional ζ-derived ITAM readily produce interleukin (IL)-2 when cross-linked with CD2-specific monoclonal antibodies (mAb). TCR-negative T cell hybridomas expressing minimal receptors consisting of an extracellular CD25 and an intracellular ζ-chain-derived segment were effectively stimulated via CD2-specific mAb. For CD2-mediated co-stimulation of TCR-negative cells, two ζ-chain-derived ITAM were sufficient to induce IL-2 when the CD2 molecules were co-cross-linked with the chimeric CD25-ζ molecules. Taken together, our results show that CD2-induced signaling does not necessarily employ the ζ-chain in TCR-positive cells and that CD2-dependent co-stimulation in TCR-negative cells can be mediated via two functional ζ-chain-derived ITAM.     

慢性HBV感染者外周血CD4+CD25high调节性T细胞初步分析

目的 分析不同临床乙型肝炎病毒(HBV)慢性感染者外周血中CD4+CD25high调节性T细胞(Treg)的水平及其与各种临床指标的关系.方法 采集35例不同临床表现成年慢性HBV感染者(HBsAb+组5例、非活动肝炎组8例、活动肝炎组12例、免疫耐受期组10例)及12例健康成人外周血标本,流式细胞仪分析外周血中CD4+CD25high Treg含量,ELISA法检测HBsAg、HBsAb、HBeAg、HBeAb、HBcAb,RT-PCR法检测HBV DNA载量,同时进行肝脏生化功能检测,并进行统计学分析.结果 HBV慢性感染者[(12.35±6.48)个/μl;(1.82 4-0.87)%)]及健康成人外周血标本[(8.91±3.11)个/μl,(1.35±0.39)%]中CD4+CD25highTreg绝对计数和其占CD4+T细胞百分含量差异均无统计学意义(P＞0.05);分组分析发现,免疫耐受期组CD4+CD25highTreg占CD4T细胞百分含量高于HBsAb+组、活动肝炎组及健康对照组(P＜0.05);免疫耐受期组CD4+CD25highTreg绝对计数高于健康对照组(P＜0.05);余各组间差异无统计学意义(P＞0.05).分析CD4+CD25highTreg含量与临床指标间相关性发现,CD4+CD25highTreg占CD4+T细胞百分含量与丙氨酸氨基转移酶(ALT)水平呈负相关(r=-0.418,P=0.038),与CD4/CD8比值呈正相关(r=0.344,P=0.021),与HBV DNA水平无相关性(r=0.118,P＞0.05);CD4+CD25highTreg绝对计数与CD4/CD8比值呈正相关(r=0.360,P=0.015),与ALT水平及HBV DNA水平无相关性(r=-0.211,r=-0.060,P＞0.05).结论 CD4+CD25highTreg在HBV慢性感染的免疫发病机制中可能发挥一定作用.     

脾切除对门脉高压症大鼠CD4、CD8和脾功能的影响

目的:研究肝硬化门脉高压症（PHT）大鼠脾次全切除术后CD4、CD8与脾功能的变化。 方法: 皮下注射60％四氯化碳复制大鼠肝硬化模型。共分5组：正常大鼠组、肝硬化（PHT）组、正常大鼠脾切除组、PHT全脾切除组、PHT脾次全切除组，每组10只。手术后第4周检测各组血常规、肝功能、tuftsin、CD4、CD8等指标。 结果:PHT高压症大鼠脾切除术后tuftsin水平［（171±21）ng/L vs （433±44） ng/L,P<0.01］、CD4/CD8（2.01±0.22 vs 1.12±0.12, P<0.01)均显著低于PHT组;PHT大鼠脾次全切除组tuftsin［（434±42）ng/L vs （171±21）ng/L, P<0.01］、CD4/CD8 （1.97±0.18 vs 1.12±0.12, P<0.01)显著高于PHT大鼠脾切除组。肝功能两者无显著差异（P>0.05）。 结论: PHT脾次全切组大鼠术后免疫和脾功能比PHT脾全切组大鼠明显改善，肝功能两者无显著变化。     

Chronic serum sickness glomerulonephritis: Passive immunisation inhibits the removal of glomerular antigen and electron dense deposits

Summary Chronic serum sickness glomerulonephritis was induced in 20 Wistar rats, using radio-labelled, chemically cationised bovine serum albumin (BSA) as antigen. Four days after the last injection of antigen, when relocation of antigen within the rat had effectively ceased, the rats were given a single large intraperitoneal dose of either non-immune rat gamma globulin or anti-BSA rat gamma globulin. Ten days later the rats were killed. The rats which had received the anti-BSA globulin had significantly more antigen in renal cortex and in isolated glomeruli than the control group. They also had larger mesangial deposits as assessed by morphometry at electron microscope level; assessment of subepithelial deposits provided equivocal results. These findings provide direct confirmation that circulating antibody which is directed against an antigen which is trapped within deposits in the glomerulus will inhibit the removal of the antigen and deposits from the mesangium.     

The thymus is a site of mast cell development in chicken embryos

Thymic mast cells were studied by light and transmission electron microscopy in chicken embryos during organogenesis. Mast cells made their first appearance at day 15. At days 16 and 17, there was a burst of mast cell development with a peak of 278 ± 54 cells/mm² at day 16. Then, mast cell density decreased until hatching. During the whole embryonic period, about 80% of mast cells localized to the thymic medulla. In the cortex, they were less numerous, and some rare mast cells could be identified in the capsule and septa. Thymic mast cells could be recognized in association with hematopoietic foci, but frequently they grew independently from areas of hematopoiesis and appeared as single cells interspersed among thymocytes, thymic epithelial cells, and interdigitating cells. They were often recognized in close relationship with the scanty and delicate extracellular matrix of the developing gland. Viewed by electron microscopy, mast cells were relatively small cells, with a few secretory granules. Exocytosis was never seen, but, notably, granules emptied in a piecemeal degranulation fashion. This study demonstrates that the chicken thymus is a site of mast cell development during embryogenesis. The high mast cell density we found suggests a possible role for these cells during thymus organogenesis.     

Mobilization and oxidative burst of neutrophils are influenced by carbohydrate supplementation during prolonged cycling in humans

Prolonged, strenuous exercise may lead to suppressive effects on the immune system, which might be responsible for a greater susceptibility to opportunistic infections. The aim of this study was to examine the influence of carbohydrate substitution (CHS) during prolonged, strenuous exercise on neutrophil granulocytes and their oxidative burst (intracellular oxidation of dihydrorhodamine₁₂₃ to rhodamine₁₂₃ after induction by formylized 1-methionyl-1-leucyl-1-phenylalanin) using flow cytometry. In three trials different concentrations of CHS (placebo compared to 6% and 12% CHS; 50 ml·kg^–1) were given randomly to 14 endurance trained cyclists [mean (SD) age 25 (5) years, maximal oxygen uptake 67 (6) ml·min^–1·kg^–1] cycling for 4 h in a steady state at 70% of their individual anaerobic threshold. Blood samples were taken before, immediately after cessation, 1 h and 19 h after exercise. A significant rise in neutrophil counts was observed immediately after cessation and 1 h after exercise with a return to normal rest values 19 h after exercise for all three conditions (P<0.001). The relative proportions of rhodamine₁₂₃+ neutrophils were significantly diminished in all three conditions 1 h after exercise (P<0.01), while the mean fluorescence intensity was lowest in the placebo trial and differed significantly to the 12% CHS trial (P=0.024) and almost significantly to the 6% CHS trial (P=0.052). In conclusion, these data suggest a beneficial effect of CHS on the neutrophil oxidative burst and a possible attenuation of the susceptibility to infections, presumably due to the reduction of metabolic stress in prolonged, strenuous exercise. Electronic Publication     

Cytokine polymorphism and its possible impact on cancer

Human cancer is an unpredictable disease as is its response to therapy. The intrinsic genetic heterogeneity and instability of cancer cells could in part explain such behavior. However, it is possible that, individual variation in the genetic make-up of humans may affect the relationship between host and cancer cells and, therefore, be, at least in part responsible for this extraordinary variation. Human gene polymorphism has been shown indeed to play a role in immune responses; among the immune-related genes, cytokines are often polymorphic. Some polymorphisms of cytokine and cytokine receptor may have direct functional significance by altering directly and indirectly the level of gene expression and/or its function; other may only demarcate a genetic linkage to a particular haplotype associated with a given clinical condition. The majority of polymorphisms found in cytokines or their receptors are located in the promoter, intronic and 3′ untranslated regions. These sequence variations can still affect gene expression and function. In this review will we summarize the current knowledge about the role of cytokine polymorphism in disease and more specifically in cancer.