Tolerogenic dendritic cells induce antigen-specific hyporesponsiveness in insulin- and glutamic acid decarboxylase 65-autoreactive T lymphocytes from type 1 diabetic patients

Tolerogenic dendritic cells (tDC) constitute a promising therapy for autoimmune diseases, since they can anergize T lymphocytes recognizing self-antigens. Patients with type 1 diabetes mellitus (T1D) have autoreactive T cells against pancreatic islet antigens (insulin, glutamic acid decarboxylase 65 -GAD65-). We aimed to determine the ability of tDC derived from T1D patients to inactivate their insulin- and GAD65-reactive T cells. CD14 + monocytes and CD4 + CD45RA- effector/memory lymphocytes were isolated from 25 patients. Monocyte-derived DC were generated in the absence (control, cDC) or presence of IL-10 and TGF-β1 (tDC), and loaded with insulin or GAD65. DC were cultured with T lymphocytes (primary culture), and cell proliferation and cytokine secretion were determined. These lymphocytes were rechallenged with insulin-, GAD65- or candidin-pulsed cDC (secondary culture) to assess whether tDC rendered T cells hyporesponsive to further stimulation. In the primary cultures, tDC induced significant lower lymphocyte proliferation and IL-2 and IFN-γ secretion than cDC; in contrast, tDC induced higher IL-10 production. Lymphocytes from 60% of patients proliferated specifically against insulin or GAD65 (group 1), whereas 40% did not (group 2). Most patients from group 1 had controlled glycemia. The secondary cultures showed tolerance induction to insulin or GAD65 in 14 and 10 patients, respectively. A high percentage of these patients (70–80%) belonged to group 1. Importantly, tDC induced antigen-specific T-cell hyporesponsiveness, since the responses against unrelated antigens were unaffected. These results suggest that tDC therapy against multiple antigens might be useful in a subset of T1D patients.     

Post-coital Contraceptive Action of Pueraria tuberosaDC. Extract in Rats

Biochemical and physiological alterations have been observed in the ovary and uterus of pregnant rats treated with an extract of Pueraria tuberosa DC. Its administration from day 1 to 5 post-coitally caused a significant increase in the wet weight, protein and glycogen contents. Activity of acid phosphatase and ATPase was depleted sharply on days 4 and 5, but the activity of alkaline phosphatase was elevated on days 4 and 5. Ovaries of treated rats showed an increased number of follicles of different age. Cells of the corpora lutea showed hypertrophy. Uterine histoarchitecture appeared nonreceptive on the day of implantation. No deciduoma was observed on day 5. These changes have been correlated with the antiimplantation action of the butanol extract.     

SGC7901-DC融合细胞疫苗表型变化特点的研究

目的利用细胞融合技术,获取SGC7901胃癌细胞-DC融合细胞疫苗,并对融合细胞表型变化进行检测,了解其变化特点,为基于树突状细胞的融合疫苗研究及应用提供实验依据.方法利用聚乙二醇(PEG)诱导SGC7901胃癌细胞、树突状细胞融合,利用HAT、HT筛选培养系统对融合细胞进行筛选培养,获取纯净融合疫苗;应用直标荧光单克隆抗体进行染色,流式细胞仪检测细胞表型变化特点.结果SGC7901胃癌细胞-DC融合后,融合细胞具备独特的形态学特点,其细胞表面分子表达较亲代DC显著升高.结论SGC7901胃癌细胞-DC融合细胞疫苗具备独特形态学特点,其细胞表面分子表达较亲代DC显著升高,成为其具备更强生物学效应的细胞学基础.     

多糖对免疫细胞调节作用的新视角 ——对树突状细胞的影响

多糖作为一种免疫调节和促进剂对巨噬细胞、T/B淋巴细胞、自然杀伤细胞(NK)和淋巴因子激活的杀伤细胞(LAK)的功能都有调节作用,树突状细胞(DC)是功能最强大的抗原提呈细胞,多糖对树突状细胞功能的影响近年来也有所报道,主要包括多糖对树突状细胞表面分子的表达、细胞因子分泌、吞噬功能、多糖受体及信号转导途径等方面的调节作用。     

树突状细胞与自身免疫的关系

树突状细胞（DC）是一类专职抗原递呈细胞（APC）,通过传导不同的调节信号调节T细胞应答或耐受。因此,DC很有可能成为免疫治疗的有力工具和靶点。近来很多数据表明DC在启动自身免疫应答中发挥重要作用。通过分析啮齿类动物和人体自身免疫病中的DC表型和DC—T细胞的相互作用可以阐明自身免疫病的部分发病机制,并且可以通过调节异常DC的功能达到免疫治疗的目的。     

正交设计考察不同干燥方法对桔梗质量的影响

目的确立桔梗的产地加工的干燥工艺。方法以药典方法并结合其他方法测定桔梗的出干率、总皂苷与水溶性浸出物的含量。结果桔梗采集后,洗净,以微波3min或80℃烘干较好,尤以微波干燥其出干率、桔梗总皂苷、水浸出物含量最高。结论通过微波干燥所得的桔梗饮片其桔梗总皂苷的含量明显高于晒干法,降低劳动强度,是一种值得研究和推广的干燥方法。     

Left ventricular false tendons in children: Prevalence as detected by 2-dimensional echocardiography and clinical significance

During a 28-month period, consecutive 2-dimensional echocardiograms were reviewed to determine the prevalence of left ventricular (LV) false tendons, their associated anomalies and clinical significance. LV false tendons were found in 31 (0.8%) of 3,847 consecutive 2-dimensional echocardiograms. Of 31 LV false tendons, 30 passed longitudinally from papillary muscle to septum and 1 went from free wall to free wall. The 31 patients were aged 1 day to 15 years. Associated heart disease, most often ventricular septal defect, bicuspid aortic valve and coarctation of the aorta, was present in 48%, of whom 73% were girls. Of those without heart disease, 69% were boys. In patients with heart disease, precordial murmurs were due to the underlying cardiac anomaly. Of those without heart disease, 15 of 16 (94%) had a precordial murmur, usually of the Still's type over the lower left sternal border. Four of 31 (13%), 1 with and 3 without heart disease, had unifocal premature ventricular contractions that were rate-dependent in the 2 patients undergoing stress testing. LV false tendons appear to occur in 0.8 % of pediatric patients and usually are accompanied by a Still's type innocent murmur if unassociated with heart disease. Some LV false tendons are associated with rate-dependent premature ventricular contractions.     

Emerging roles of basophils in allergic inflammation

Basophils have long been neglected in immunological studies because they were regarded as only minor relatives of mast cells. However, recent advances in analytical tools for basophils have clarified the non-redundant roles of basophils in allergic inflammation. Basophils play crucial roles in both IgE-dependent and -independent allergic inflammation, through their migration to the site of inflammation and secretion of various mediators, including cytokines, chemokines, and proteases. Basophils are known to produce large amounts of IL-4 in response to various stimuli. Basophil-derived IL-4 has recently been shown to play versatile roles in allergic inflammation by acting on various cell types, including macrophages, innate lymphoid cells, fibroblasts, and endothelial cells. Basophil-derived serine proteases are also crucial for the aggravation of allergic inflammation. Moreover, recent reports suggest the roles of basophils in modulating adaptive immune responses, particularly in the induction of Th2 differentiation and enhancement of humoral memory responses. In this review, we will discuss recent advances in understanding the roles of basophils in allergic inflammation.     

Ammonium accumulation and chemokine decrease in culture media of Gcdh−/− 3D reaggregated brain cell cultures

Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain.We analyzed morphological and biochemical features of 3D brain cell aggregates issued from Gcdh^?/? mice at two different developmental stages, day-in-vitro (DIV) 8 and 14, corresponding to the neonatal period and early childhood. We also induced a metabolic stress by exposing the aggregates to 10 mM l-lysine (Lys).Significant amounts of GA and 3-OHGA were detected in Gcdh^?/? aggregates and their culture media. Ammonium was significantly increased in culture media of Gcdh^?/? aggregates at the early developmental stage. Concentrations of GA, 3-OHGA and ammonium increased significantly after exposure to Lys. Gcdh^?/? aggregates manifested morphological alterations of all brain cell types at DIV 8 while at DIV 14 they were only visible after exposure to Lys. Several chemokine levels were significantly decreased in culture media of Gcdh^?/? aggregates at DIV 14 and after exposure to Lys at DIV 8.This new in vitro model for brain damage in GA-I mimics well in vivo conditions. As seen previously in WT aggregates exposed to 3-OHGA, we confirmed a significant ammonium production by immature Gcdh^?/? brain cells. We described for the first time a decrease of chemokines in Gcdh^?/? culture media which might contribute to brain cell injury in GA-I.