简介：IntroductionAsoneofthemostfrequentlydiagnoseddevastatingdiseases,liverfailureisresponsibleforapproximatelytwomilliondeathsannuallyworldwidewithpoorprognosis1.Althoughlivertransplantationhasbeendevelopedforthemosteffectivetreatmentforliverfailure,itisfarfromdemandsforpatientsduetotheshortageofhigh-qualitydonorliversandexpensivetreatmentcosts.Currently,withthedevelopmentofcelltherapy,celltransplantationsincludingprimaryhumanhepatocytes(PHHs),humanhepatocyte-likecells(HLCs)andliverorganoidsareemergingasgreatpotentialtoolstoalleviatethisgrowingburden.

简介：在allogeneic干细胞移植(SCT)，缺乏他们的血缘的禁止的ligand的生来的杀手(NK)房间能导致graft-versus-leukemia回答，没有严重graft-versus-host疾病(GVHD)的正式就职。这个特征能为细胞的免疫疗法被利用。在这研究，我们检验了在整个人的外部血NK房间人口以内表示不同漂亮像免疫球蛋白的受体(KIR)的NK房间子集的选择扩大，面对HLA-Cw3(C1)或Cw4(C2)transfectedK562激发器房间。有C1或C2的KIR+NK房间的Coculture积极K562房间，面对IL-2+；IL-15，触发了错过了他们的血缘的ligand的NK房间的长出。这在整个NK房间人口以内导致了alloreactiveKIR+NK房间的增加的频率。在有缺乏他们的血缘的ligand的K562房间的preculture以后，当时，另外，我们观察到这张alloreactiveNK人口揭示了CD107+房间的更高的数字有相关K562HLA-Ctransfected目标房间的cocultured，作为与有untransfectedK562房间的coculture相比。这提高的反应作为目标用主要白血病的房间被证实。这研究证明那HLA一级表情能调停扭曲NK房间全部剧目并且向白血病的目标房间与提高的alloreactivity为房间充实人口。这个特征可以支持未来NK基于房间的免疫疗法的临床的应用。

简介：贡献体液调停allograft拒绝的分子的小径糟糕被定义。在这研究，我们估计了在调停抗体的allograft拒绝的上下文表明小径的herpesvirus入口mediator/B淋巴细胞和T淋巴细胞衰减器(HVEM/BTLA)的角色。一个试验性的背景被设计阐明HVEM/BTLA相互作用的封锁是否能调制感应的denovo在接枝拒绝的功课期间招待antidonor特定的抗体。测试这个假设，充分allogeneic专业histocompatibility错配建筑群的皮肤接枝被移植到与适应于不同地区生活的动物控制，anti-CD40L或发信号的HVEM/BTLA的调节抗体被对待的接受者老鼠的正确胁腹上小径。CD4的频率T小囊的助手(Tfh)房间(B220，CD4+CXCR5+PD-1high)，extrafollicular助手房间(B220，CD4+CXCR5PD-1+和PD-1)并且幼芽的中心(GC)B房间(B220+Fas+GL7+)被流动cytometry在在接枝拒绝的尖锐阶段期间在白天10柱子移植排干和非排干的淋巴节点分析。适应于不同地区生活的动物特定的体液的有免疫力的反应也是的主人antidonor估计了。而CD40/CD40L小径的封锁在阻止allogeneic是高度有效的体液的有免疫力的反应，HVEM/BTLA-interacting小径的调停抗体的封锁影响了Tfh房间的既不扩大也不GCB房间的扩大。因而，主机antidonor的功课调停抗体的反应通常继续了，没有损害开发的可检测的证据。在摘要，这些数据显示HVEM/BTLA相互作用为denovo主人antidonor的形成是非必需的在移植的适应于不同地区生活的动物特定的抗体。

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简介：IL-12priming在CD8+受动器T房间的刺激和CD8+记忆T(Tm)房间的开发起一个重要作用。然而，房间当IL-12priming不在时开发了的CD8+Tm的功能的改变是elusive.In这研究，我们调查了房间从转基因的OT开发了的CD8+Tm的第二等的扩大的能力我CD8+T房间。后者房间在vitro并且在ovalbumin(卵)刺激的vivo是-puised树枝状的房间[DCOVA并且(IL-12-/-)DCOVA]分别地源于野类型的C57BL/6和IL-12基因大美人老鼠。我们证明IL-12priming在CD8+T房间是重要的不仅同种细胞的扩大，而且在有在抗原再相遇之上的第二等的扩大的能力的CD8+Tm房间的产生。然而，发信号的IL-12不涉及CD8+Tm房间幸存和召回回答。因此，这研究为疫苗的设计和开发提供有用信息。

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简介：人工的介绍抗原的房间被期望在注入前刺激T房间的最佳的治疗学的特征的扩大和获得。这里，绑在IgGmonoclonal抗体的可结晶的碎片的CD32遗传上在人的K562白血病房间上被表示为T房间受体提供ligand。CD86和4-1BBL，它是分别地，CD28和4-1BB的受体是的共同刺激的ligands也在K562上表示了房间。然后，我们由对CD3与OKT3monoclonal抗体联合K32/CD86/4-1BBL房间完成了人工的介绍抗原的房间，命名K32/CD86/4-1BBL/OKT3房间。这些人工的修改细胞有导致CD8+T细胞激活的能力，支持CD8+T细胞增长，分割，和长期的生长，禁止CD8+T细胞apoptosis，并且提高IFN-和perforin的CD8+T细胞分泌物。而且，抗原特定的细胞毒素的T淋巴细胞能在至少在28天以内与K32/CD86/4-1BBL/OKT3房间刺激的文化被保留。这条途径为CD8+T房间的扩大和激活柔韧、简单、可再现、节俭并且可以为采纳免疫疗法有重要治疗学的含意。

简介：AbstractBackground:To date, there is only scare evidence characterizing the temporal features and progression of metabolic dysfunction in high-fat diet (HFD)-fed obese mice. Hence, its specific pathogenesis remains unclear.Methods:Sixty 6-week-old male C57BL/6J mice were randomly divided into HFD and control diet (CD) groups and sacrificed at 1, 5, 9, 13, 17, and 21 weeks, respectively. At weekly intervals, intraperitoneal glucose tolerance testing (IPGTT) and intraperitoneal insulin tolerance testing (IPITT) were performed in both groups. A detailed time course in HFD-fed mice was investigated by evaluating the initiation of glucose homeostasis impairment, dyslipidemia, systemic insulin sensitivity, monocyte chemoattractant protein-1 (MCP-1) levels, epididymal white adipose tissue (eWAT) expansion, macrophage content changes, proinflammatory (M1)/anti-inflammatory (M2) macrophage imbalance, lipid accumulation in the liver, and β-cell morphometry in the pancreas.Results:In the HFD group, progressive weight gain and impairments in glucose metabolism (elevated fasting blood glucose and area under the curve (AUC) of IPGTT) were observed from the 3rd week, and a significantly elevated AUC of IPITT was first detected after week 7 of HFD feeding. As for dyslipidemia, after 9 weeks of feeding, the low-density lipoprotein cholesterol level and total cholesterol level in HFD group were significantly higher than those in the CD group (all P < 0.05), whereas no significant differences were shown in triglyceride level. Adipocyte size increased significantly in the HFD group in the 1st week, a phenotypic switch in eWAT from anti-inflammatory (M2) to pro-inflammatory (M1) macrophages was observed in the 5th week, and the metabolic inflammation was distinct in eWAT in the 9th week. Additionally, liver steatosis was considerably obvious at the 17th week and pancreatic β-cell morphometry did not change during 21 weeks of HFD feeding.Conclusion:The eWAT expansion was detected early in HFD-induced obese mice, which occurred prior to obvious insulin resistance.