Polymorphism A/G in Position +49 of CTLA4 Exon 1 in Multiple Sclerosis in Russians

The association of multiple sclerosis (MS) with alleles A and G of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a candidate gene for autoimmune disorders, was studied. The allele polymorhism results from single nucleotide substitution (A/G) in position +49 of exon 1 and leads to substitution Thr Ala in the leader peptide. The case–control study involved two groups of ethnic Russians: 168 MS patients and 209 healthy subjects from central Russia. Genotype frequencies were in agreement with the Hardy–Weinberg equilibrium in both groups (P > 0.05). The controls significantly differed in CTLA4 allele and genotype frequencies from Mongoloids but not from other Caucasians. No association was observed between MS and CTLA4. In addition, the combined association with MS was analyzed for both the CTLA4 alleles and allele groups of HLA DRB1. The results showed that the CTLA4 dimorphism does not affect susceptibility to MS in ethnic Russians, be these stratified or not with regard to DRB1 alleles corresponding to serologic specificities DR1 to DR16.     

急性低氧和腺苷对大鼠脾脏T淋巴细胞增殖的影响

目的:观察急性低氧和腺苷对大鼠脾脏T淋巴细胞增殖的影响,以探讨急进高原时机体免疫功能改变的规律和机制.方法:大鼠在5 000 m模拟高原减压低氧3 d后,用3H-TdR掺入法检测脾脏T淋巴细胞增殖功能,增加细胞培养液中腺苷浓度观察对T淋巴细胞增殖的影响.结果:在5.0 mg/L 和2.5 mg/L刀豆素A(concanavalin A,ConA)的刺激下,对照组大鼠脾脏T淋巴细胞的刺激指数分别为64.0±23.7和43.5±21.7;急性低氧组大鼠显著降低至29.4±11.3 和20.2±16.1;10 μmol/L和100 μmol/L腺苷能够显著抑制大鼠脾脏T淋巴细胞的增殖反应,且这种抑制作用具有明显的浓度依赖性.结论:急性低氧可在一定程度上抑制T淋巴细胞功能,这种抑制作用可能与低氧引起的腺苷含量增加有关.     

Simplifying the phytohaemagglutinin skin-testing technique in studies of avian immunocompetence

1. Researchers involved in ecology and toxicology, as well as many other aspects of avian biology, use phytohaemagglutinin (PHA) skin testing as a means of evaluating the immune status of individuals.
2. Immune function, one measure of individual quality, can be used as a sensitive, non-lethal variable that may be negatively affected in animals exposed to degraded, contaminated or otherwise disturbed ecological zones.
3. Typically this test has been applied by challenging one wing web with the immunostimulant PHA, while the other 'control' wing is injected with phosphate buffered saline (PBS). Injection sites on the wing web are measured before and 24 h after injection with PHA or PBS. The immune response is considered to be the difference between the two wings.
4. Results from PHA skin tests conducted on 608 birds in seven studies representing passerines, waterfowl, upland game birds and raptors are examined.
5. Numerous advantages to eliminating the PBS injection as the experimental control are: (i) decrease by half, the time required for testing; (ii) decrease handling-related stress on the birds (proportional to handling time); (iii) reduce the probability of errors at injection time; (iv) spare the other wing for different tests or uses (e.g. tuberculin DTH testing); and (v) decrease the coefficient of variation that is due to measurement inaccuracies.
6. The only disadvantage identified is that hypersensitive individuals (outliers) could be missed, which in this case represents 2 of 608 individuals.     

Enhancement of immunotherapeutic effects of HPV16E7 on cervical cancer by fusion with CTLA4 extracellular region

Cervical cancer is caused by infection by high-risk human papillomavirus (HPV), especially HPV16. Limitations in current treatments of cervical cancers call for the development of new and improved immunotherapies. This study aims at investigating the efficacy of a novel vaccine consisting of modified HPV 16E7 fused with human cytotoxic T-lymphocyte antigen 4 (CTLA4). The regions in HPV16 E7 gene associated with its transformation and CTL-enhanced response were modified; the resultant HPV16mE7 was fused with extracellular region of CTLA4 to generate HPVml6E7-eCTLA4 fusion protein. Binding of this fusion protein to B7 molecules expressed on antigen presenting-cells (APCs) was demonstrated. C57BL/6 (H-2^b) mice immunized with low dose of the fusion protein (10 μg) produced higher titer antibody and stronger specific CTL response, and expressed higher levels of IFN-γ and IL-12, compared with those immunized with HPVml6E7 only or admixture of HPVml6E7 and CTLA4, or PBS; and were protected from lethal dose tumor challenge. Tumor growth was retarded and survival prolonged in mouse models with the fusion protein treatment. Our results demonstrate that fusion of HPV16 E7 with eCTLA4 targeting APCs resulted in enhanced immunity, and that this fusion protein may be useful for improving the efficacy of immunotherapeutic treatments of cervical cancer and other HPV16 infection-associated tumors.     

The immune enhancement of propolis adjuvant on inactivated porcine parvovirus vaccine in guinea pig

Two experiments were carried out. In immune response test, the immune enhancement of propolis, oilemulsion and aluminium salt were compared in guinea pig vaccinated with inactivated porcine parvovirus (PPV) vaccine. The result showed that three adjuvants could enhance antibody titer, T lymphocyte proliferation, IL-2 and IL-4 secretion of splenic lymphocyte. The action of propolis was similar to that of oilemulsion and superior to that of aluminium salt, especially in early period of vaccination propolis could accelerate antibody production. In immune protection test, the effects of three adjuvants on PPV infection were compared in guinea pig vaccinated with PPV vaccine then challenged with PPV. The result showed that propolis and oilemulsion could enhance the antibody titer, IL-2 and IL-4 content in serum and decrease the PPV content in blood and viscera. In the effect of improving cellular immune response, the propolis was the best. These results indicated that propolis possessed better immune enhancement and would be exploited into a effective adjuvant of inactivated vaccine.     

CTLA-4+49A>G基因多态性与结直肠癌的相关性研究

目的:探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)+49 AG位点多态性与结直肠癌发生的相关性,为早期预测结直肠癌的发生提供临床参考依据。方法:选取结直肠癌病例231例未实验组和正常健康体检者325例为对照组,取其空腹外周静脉血提取DNA后,采用聚合酶链式反应(PCR)技术对CTLA-4基因第1外显子区+49位点DNA进行扩增,产物用限制性片段长度多态性(RFLP)方法检测CTLA-4第1外显子区+49AG位点的多态性,比较两组杂合子AG和纯合子AA、GG基因型发生的频率、A等位基因与G等位基因的分布,分析CTLA-4+49 AG位点多态性与结直肠癌发生的相关性。结果:两组间CTLA-4基因外显子1区+49AG位点杂合子AG和纯合子AA、GG基因型发生的频率以及A等位基因与G等位基因的分布比较差异均无统计学意义(P0.05)。结论:CTLA-4基因外显子1区+49 AG基因多态性与我省汉族人群结直肠癌的发病无显著相关性。     

吲哚胺2,3-双加氧酶基因转染对肝癌细胞凋亡的影响及相关机制研究

目的:通过细胞培养和在体实验探讨吲哚胺2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)基因转染后对肝癌细胞凋亡的影响及相关细胞免疫机制的研究.方法:提取健康人外周血中的T细胞利用细胞培养和基因转染技术将T细胞和肝癌细胞混合培养.实验分为6组:根据是否加入D-1-MT分为未干预组和干预组...     

中西医联合治疗慢性再生障碍性贫血临床观察

目的:探讨中药血复生联合西药治疗慢性再生障碍性贫血(CAA)的临床效果,及对造血、细胞免疫功能和血清IL-2、IFN-γ的影响。方法:将54例慢性再生障碍性贫血分为联合治疗组与对照组,其中对照组给予西药常规治疗,联合治疗组在此基础上加用血复生,通过观察治疗前后患者临床症状、外周血象、T-淋巴细胞亚群和血清IL-2、IFN-γ水平变化,比较两组疗效。结果:联合治疗组总有效率为88.24%,显著高于对照组65.00%的总有效率(P<0.01),联合治疗组在症状改善、升高全血细胞、调节T-淋巴细胞亚群和降低血清IL-2、IFN-γ水平等方面作用优于对照组(P<0.01或0.05),且不良反应少。结论:血复生联合西药可促进CAA患者造血细胞增殖,调节细胞免疫功能,效果好于单用西药。     

In vivo iron and zinc deficiency diminished T- and B-selective mitogen stimulation of murine lymphoid cells through protein kinase C-mediated mechanism

Zinc and iron are crucial mineral components of human diet, because their deficiency leads to several disorders, including alterations of the immune function. It has been demonstrated, in both humans and rodents, that a diminished number of lymphoid cells and a loss of lymphocyte activity accompany deprivation of these essential minerals. The aim of this work was to analyze if iron and/or zinc imbalances regulate lymphocyte activity and the intracellular signals involved in the effect. Mice from the BALB/c strain were fed with iron- and/or zinc-deficient or mineral-supplemented diets, according to the American Institute of Nutrition Rodent Diets. Levels of iron and zinc were assessed in blood, liver, or bone samples. Selective mitogen stimulation of T- and B-lymphocytes were performed. We found a diminished proliferative response in T- and B-lymphocytes from zinc- and/or iron-deficient animals with respect to controls. These effects were related to decreased mitogen-induced translocation of protein kinase C (PKC) activity to cell membranes on both cell types from all animals fed with deficient diets. Our results demonstrate that iron and zinc deficiencies affect both T- and B-lymphocyte function by PKC-dependent mechanisms.