复发性口腔溃疡免疫细胞的效应

复发性口腔溃疡是口腔科常见多发性疾病,与多种因素导致的自体免疫失衡有关。表现为免疫细胞活性和数量上的改变,特别是高表达或不正常表达CD4+、 CD8+细胞以及 CD4+/ CD8+的改变,并伴有多种细胞因子的变化,包括 IL-2 、IL-6、IL-8﹑IL-10、INF-γ 和TNF-α等多种细胞因子的异常表达以及相关细胞因子的基因突变导致的基因多态性。T淋巴细胞介导的细胞免疫在复发性口腔溃疡疾病的发生、发展过程中起重要作用。     

Synthetic immunostimulatory oligonucleotides in experimental and clinical practice

BackgroundOligonucleotides belong to a class of macromolecules with great potential for research and various therapeutic applications. Their mechanisms of action are extremely diverse, although they are rather homogeneous in composition. Single-stranded oligodeoxynucleotides are not only inhibitors of gene expression, but their CpG sequence motifs may activate the innate immune response. Recent progress made in preclinical and clinical testing, as well as the case of the most recently discovered RNA interference technology, will help to overcome efficacy problems of the previous approaches of the ‘standard therapy’ of such diseases as tumors and various infections.MethodsThe aim of this article is to present various therapeutic aspects of oligonucleotides, and to review the most significant therapeutic applications of synthetic oligonucleotides. This paper presents a comprehensive review of current literature on various therapeutic properties of synthetic oligonucleotides.ConclusionsThe available results gathered from preclinical and clinical studies suggest that TLR9-targeted therapy of oligonucleotides can stimulate both innate and adaptive immunity. It also appears that CpG ODNs are generally safe, although moderate adverse effects, based on a backbone-related mechanism have been reported. The presented studies demonstrate that adjuvant CpG ODN can unify an immune response that leads to enhanced antigen-specific Ab formation. CpG ODN may therefore provide a unique approach to enhancing the efficacy of immunization, including the strengthening of antitumor immunity.     

Statins can induce myasthenia gravis

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are commonly prescribed for prevention of cardiovascular morbidity. A rare side effect of statin medication is the induction of autoimmune illnesses, including myasthenia gravis (myasthenia). Here we present two patients with seropositive myasthenia that developed 4 weeks after initiation of atorvastatin, increasing the total reported patients to seven. Reviewing recent literature we highlight the connections between statins, auto-immunity and myasthenia. Statins may favour T-cell phenotypes that reduce cell-mediated immunity but could increase antibody-mediated humoral immunity.     

Treponemal antibody in CSF and cellular immunity in peripheral blood of syphilitic patients with persisting positive rapid plasma regain

The ratio of patients with RPR constant positive more than 2 years despite receiving standard syphilis treatment has been reported to be 11.54%~31.3%. The current interpretations on this phenomenon are cellular immune function restrained and the existence of neurosyphilis or asymptomatic neurosyphilis. We conducted this study to detect the treponemal antibody in cerebrospinal fluid (CSF) and lymphocyte subsets in peripheral blood of syphilis patients with persisting RPR positive more than 2 years without neurologic signs, and then explore their relationship. In this study, Treponemal antibody in CSF of 46 syphilitic with HIV negative were measured by syphilis serum test and compared with that of 5 neurosyphilis. Lymphocyte subsets were measured by flow cytometry (FCM) and compared with that of 30 healthy controls. We observed that treponemal antibody in CSF was detected not only in 12 cases (25.21%) of 46 treated patients, but also in 5 neurosyphilis. The ratio of lymphocyte subsets revealed that CD3⁺, CD4⁺ T cells and natural killer (NK) cells showed no significant differences between the patient and healthy controls (P > 0.05), while CD8⁺ T cells in patients were significant higher than that in healthy controls (P < 0.001). Lymphocyte subsets showed no significant differences between the patients with treponemal antibody positive and negative in CSF (P > 0.05). In conclusion, the treponemal antibody in CSF of treated patients suggests that part of them were asymptomatic neurosyphilis and with cellular immunodifeciency. And there is no significant relationship between asymptomatic neurosyphilis and cellular immunodeficiency in peripheral blood.     

Cytotoxic T-Lymphocyte Antigen-4 Single Nucleotide Polymorphisms Are Not Associated with Outcomes after Unrelated Donor Transplantation: A Center for International Blood and Marrow Transplant Research Analysis

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays an essential role in T cell homeostasis by restraining immune responses. AG and GG genotypes of donor CTLA-4 SNP rs4553808 in patients after unrelated donor hematopoietic stem cell transplantations (HSCT) have been shown to be an independent predictor of inferior relapse-free survival (RFS) and overall survival (OS) compared with those with the AA genotype, in single-center studies. We tested the hypothesis that SNP rs4553808 is associated with RFS, OS, nonrelapse mortality (NRM) and the cumulative incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in adults with acute myeloid leukemia and advanced myelodysplastic syndrome undergoing a first 8/8 or 7/8 HLA-matched unrelated donor HSCT. Multivariable analysis adjusting for relevant donor and recipient characteristics showed no significant association between SNP rs4553808 and OS, RFS, NRM, and incidence of acute and chronic GVHD. An exploratory analysis of other CTLA-4 SNPs, as well as studying the interaction with antithymocyte globulin, also demonstrated no significant associations. Our results indicate that CTLA-4 SNPs are not associated with HSCT outcomes.     

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef’s influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef’s ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor.     

Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus

Summary Humoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset < 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3⁺: 58.1 ±8.5% versus 70.7±8.0%), helper/inducer cells (OKT4⁺: 33.8 ±7.0% versus 47.1 ±8.3%), suppressor/cytotoxic cells (OKT8⁺: 18.5±7.3% versus 32 ± 6.8%) and monocytes (OKM1⁺: 11.5±3.8% versus 19.9±5.2%) (p< 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p< 0.01–0.05). The helper/suppressor ratio (OKT4⁺/OKT8⁺) was higher in newly diagnosed patients than in control subjects (2.2±1.3 versus 1.5±0.3; p< 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8⁺ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Our data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8⁺ and OKT4⁺ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.     

CHC患者外周血T细胞免疫功能与丙型肝炎病毒表达的关系

目的 探讨慢性丙型肝炎(CHC)患者外周血T细胞免疫功能与丙型肝炎病毒(HCV)复制及核心抗原(HCV-cAg)表达的关系.方法 采用流式细胞术、荧光定量PCR和ELISA对63例健康体检者(对照组)和85例CHC患者(CHC组)的外周血T淋巴细胞亚群、血清HCV-RNA和HCV-cAg进行测定.结果 CHC组总T细胞、T4细胞、T8细胞、双阴性细胞(DNT )、双阳性细胞(DPT )水平依次为(67 .37 ± 10 .43)% 、(37 .11 ± 10 .28)% 、(21 .63 ± 8 .87)% 、(7 .80 ± 4 .57)% 、(0 .20 ± 0 .29)% ,T4/T8比值为(2 .18 ± 1 .26 )% ,绝对水平依次为(0 .70 ± 0 .44 ) × 109/L、(0 .37 ± 0 .22 ) × 109/L、(0 .22 ± 0 .17 ) × 109/L、(0 .08 ± 0 .06 ) × 109/L和(0 .19 ± 0 .68)× 107/L ;CHC患者T8细胞水平显著减少(P＜0 .01) ,致使T4/T8比值升高(P＜0 .05);CHC患者总T细胞、T4细胞、T8细胞和DNT的绝对值均显著减少(P＜0 .05);HCV-RNA和 HCV-cAg阳性时 ,T4细胞和DNT 水平显著升高(P＜0 .05).结论 CHC患者 HCV复制表达时 ,患者 T细胞亚群存在明显异常 ,T细胞免疫功能低下或免疫耐受是CHC迁延难愈的重要原因.     

高效抗逆转录病毒治疗15例人类免疫缺陷病毒感染者一年总结

目的 首次报道我国于1999年5月开始对人类免疫缺陷病毒（HIV）－1感染者的规范化高效抗逆转录病毒治疗。方法 用齐多夫定＋拉米夫定（AZT＋3TC,商品名：双汰芝）联合硫酸茚地那韦（indinavir,商品名：佳息患）对15例HIV感染或艾滋病患者进行为期1年的治疗。随访指标为病毒载量和T淋巴细胞亚群分析。结果 15例随访1年,用药3个月后HIV－1 RNA平均值至198拷贝／ml,比治疗前的90743RNA拷贝／ml下降2.7log。用药后12个月CD4细胞计数平均增加67个／μl,CD8细胞计数平均减少192个／μl,CD4／CD8比例从0．35增加到0．56,15例中2例未作T淋巴细胞亚群分类,13例治疗后3、6、9、12个月CD4^ 童贞细胞（CD45RA＋CD62L＋）数呈现平稳上升趋势,在治疗1年时平均升高42个／μl。而CD8^ 童贞细胞（CD45RA＋CD62L＋）数平均升高19个/μl。所有患者用药后出现消化道反应,3例出现一过性黄疸,2例出现泌尿系结石。结论 与国外临床报道的治疗效果相一致,15例HIV－1不同阶段感染者经治疗后病毒载量水平明显降低,CD4平均细胞数有所增加,在具有不同病毒基因亚型的病例显示同样的治疗效果。