简介:因为他们的能力,B房间通常被认为是有免疫力的反应的积极管理者生产抗体,包括自身抗体。因为B房间用作介绍抗原的房间并且在有免疫力的回答施加另外的调节功能,抗体的生产便于最佳的CD4+T房间激活。然而,某些B房间能否定地也由生产规章的cytokines并且直接经由cell-to-cell接触与病原的T房间交往调整有免疫力的反应。B房间的这些类型被定义为规章的B(Breg)房间。Breg房间的规章的函数在发炎的鼠标模型被表明了,癌症,移植,并且特别地在autoimmunity。在这评论,我们集中于在人的自体免疫的疾病导致发展的理解和Breg房间的功能和B房间的含意的最近的进展。
简介:ImmunizationwithinactivatedautoreactiveTcells(Tcellvaccination)selectedfromindividual'sownTcellrepertoireprovidesauniqueinvivosettingfortestingimmuneregulationthatisknowntoinvolveinteractionsofavarietyofrelatedsurfacemolecules(1).ItinducesregulatoryimmuneresponsesthatcloselyresembletheinvivosituationwheretheimmunesystemischallengedbyclonalactivationandexpansionofgivenTcellpopulationsinvariousautoimmunediseases.TcellvaccinationprovidesapowerfulmeansofelicitingnaturalreactionsoftheimmunesysteminresponsetoclonalexpansionofTcells,whichcanusedasatherapeuticapproachtosuppressoreliminatespecificpathogenicautoreactiveTcellsinautoimmuneconditions.ClinicaltrialsusingTcellvaccinationtodepleteautoreactiveTcellsinhumanautoimmuneconditionshavebeguntorevealthepathologicrelevanceofvariousautoimmuneTcellpopulationsinthediseaseprocesses,providingauniqueopportunitytotesttheautoimmunetheoriesinaclinicalsetting.Cellular&MolecularImmunology.2004;1(5):321-327.
简介:通过ubiquitin-proteasome系统的蛋白质降级是细胞内部的蛋白质的non-lysosomal解朊作用的主要小径。它在象房间周期的规定那样的许多基本细胞的过程起重要作用有免疫力、煽动性的回答的前进,分割,开发和区别,apoptosis,房间trafficking,和调整。这个系统的中央元素是到指向的蛋白质的ubiquitin的连接,它是然后由26Sproteasome认出了的共有原子价,腺苷triphosphate依赖的、多催化的朊酶。损坏,氧化,否则象控制许多批评细胞的函数的规章的蛋白质一样的错误褶层蛋白质在这降级进程的目标之中。这个系统的错误导致细胞的动态平衡的dysregulation和多重疾病的发展。在这评论,我们在煽动性、自体免疫的疾病的开发描述了基本生物化学和ubiquitin-proteasome系统,和它的复杂角色的分子的生物学。另外,与ubiquitin-proteasome系统有关的治疗和潜在的治疗学的目标也被讨论。细胞与分子的免疫学。2006;3(4):255-261。
简介:TheJanuskinase-signaltransducersandactivatorsoftranscription(JAK-STAT)signalingpathway,activatedbymorethan50cytokinesorgrowthfactors,playscriticalrolesinawidevarietyofcellularfunctionsinthehematopoietic,immune,neuronalandhepaticsystems.Intheliver,thissignalingpathway,activatedbymorethan20cytokines,growthfactors,hormones,andhepatitisviralproteins,playscriticalrolesinantiviraldefense,acutephaseresponse,hepaticinjury,repair,inflammation,transformation,andhepatitis.ThisarticlereviewsthebiologicalsignificanceofSTAT1,2,3,4,5,6inhepaticfunctionsanddiseases.Cellular&MolecularImmunology.2005;2(2):92-100.
简介:ToinvestigatethesignificanceoftheSARS-associatedcoronavirus(SARS-CoV)antibody,detectedbyELISAandindirectimmunofluorescenceassays(IFA)fortheSARS-CoVVeroE6celllysates,innon-SARSsubjects,114serumsamplesfromhealthycontrolsand104serumspecimensfromautoimmunediseasepatientswerecollected.TheresultsofELISAshowedthatamong114serafromhealthycontrols,4(3.5%)werepositiveofSARS-CoV-IgGantibodyand114(100%)wereallnegativeofSARS-CoV-IgMantibody;thespecificityofSARS-CoV-IgGantibodyforSARSpatientswas96.5%,butthespecificityofbothSARS-CoV-IgGand-IgMantibodiesforSARSpatientswas100%.In58caseswithSLE,positiveratesofSARS-CoV-IgGand-IgMantibodieswere32.8%(19/58)and8.6%(5/58),respectively,inwhich11cases(19%)werepositiveofbothSARS-CoV-IgGand-IgMantibodies;in10caseswithSS,positiverateofbothSARS-CoV-IgGand-IgMantibodieswas10%(1/10);in16caseswithMCTD,positiverateofSARS-CoV-IgGwas37.5%(6/16),positiverateofbothSARS-CoV-IgGand-IgMantibodieswas6.3%(1/16);in20caseswithRA,onecasewaspositive(5%)ofSARS-CoV-IgG.However,ofallsampleswithpositiveSARS-CoV-IgGand-IgMantibodiesforautoimmunediseasesandhealthycontrols,SARS-CoVRNAandantibodieswereallnegativebyRT-PCRandIFA.AllserafornegativeorpositiveELISAresultswerealsonegativeorpositiveresultsusingELISAwithVeroE6cellslysates.ThesestudiesshowedthatSARS-CoVVeroE6celllysatesfortheELISAtodetectSARS-CoVantibodiescouldleadtothefalse-positivereactionsorcross-reactionsofSARS-CoVantibodiesinnon-SARSdiseasesandhealthycontrols,andthefalse-positivereactionsorcross-reactionswererelatedtoVeroE6celllysatesandautoantibodiesinnon-SARSpopulation.
简介:Toinvestigatetheexpressionofapoptosis-relatedprotein(Fas,FasL,andBcl-2)inthepathogenesisofautoimmunethyroiddisorders(ATDs),immunohistochemicalstainingwasperformedon20Hashimoto'sthyroiditis(HT),20Graves'disease(GD),and20thyroidfollicularadenoma(TFA,ascontrol).AllthecasesexpressedFas,mainlyonthecellsurfaceandcytoplasm.FasLwasfoundin17casesoftheTFA.Bcl-2wasdetectedin15casesofHT,19ofGDand17ofTFA.InTFA,amoderateFasexpressionandaminimalornoFasLexpressionwasdetectedonfollicularcells.InHT,thefolliclesadjacenttoinfiltratinglymphocytesshowedincreasedlevelsofFasandFasLexpression.AweakerstainingofFasandFasLwasexhibitedoninfiltratinglymphocytesthanonthyrocytes.InacomparisonofGDwithHT,thyrocytesandlymphocytesshowedsimilarFasstaining,butforFasLthestainingwasratherweakerinHT.TheexpressionofBcl-2wasnearlyidenticalinGDandTFA,butmuchweakeronthefollicularcellsinvicinityoflymphocytesandonthelymphocyteslocatedingerminalcentersofHTtissues.TheexpressionofFas,FasL,Bcl-2inHashimoto'sthyroiditisandGraves'diseasewerealmostsame.FasLstrongexpressionandBcl-2weakexpressiononthefolliclesinHTmayinduceapoptosis.TheseresultsprovidedevidenceforexpressionofFas,FasLandBcl-2inthepathogenesisofautoimmunethyroiddisease.ThelymphocytesseemnottobedirectlyengagedintheprocessviatheirownFasL,buttheymayprovidesomecytokinesthat,inturn,upregulateFasand/orFasLexpressiontoinduceapoptosis.
简介:Polyreactive天生类型的B房间说明在圆周表示自我反应的许多B房间。这些B房间的不适当的规定可以是位于自体免疫的疾病下面的一个重要因素。这里,我们在导致骨胶原的关节炎(中央情报局)的开发探索了自我反应的天生的B房间的影响,风湿性关节炎的一个鼠标模型。我们显示出那个脾的边缘的地区(MZ),然而并非B-1B房间在naı展出自发的IgM反应到自体同源的骨胶原II;¨;ve老鼠。在有在完全的Freund’的heterologous骨胶原II的免疫之上;骨胶原反应的MZB房间很快扩展了的s助手,当B-1B房间显示出谦虚反骨胶原回答时。MZB房间被像使用费的受体(TLR)容易激活4并且在vitro,导致的增长和cytokine分泌物的9-ligands,暗示B房间受体和TLR的那个双约会可以把有免疫力的反应提升到自我抗原。而且,告知骨胶原的MZB房间显示出在vivo在IgG反骨胶原抗体的vitro和正式就职由血缘的T房间增长思考了的重要介绍抗原的能力。在1和2表明了的补充受体是缺乏的MZB房间增加了增长和cytokine生产,当时Fcγ;房间的受体IIb缺乏导致增加的cytokine生产和抗原表示。在结论,我们的数据在中央情报局作为自体免疫的反应的开始者加亮自我反应的MZB房间,在补充和Fc受体在在房间控制自我反应是相关的的地方。
简介:CD3-specificmonoclonalantibodywasthefirstoneusedforclinicalpracticeinfieldoftransplantation.Recently,renewedinterestshaveelicitedinitscapacitytopreventautoimmunediabetesbyinducingimmunetolerance.Inthisstudy,wetestedwhetherthisantibodycanalsobeusedtotreatanotherkindofautoimmunediseasemyastheniagravis(MG)andexploredthepossiblemechanisms.MGiscausedbyanautoimmunedamagemediatedbyantibody-andcomplement-mediateddestructionofAChRattheneuromuscularjunction.WefoundthatadministrationofCD3-specificantibody(Fab)2toananimalmodelwithexperimentalautoimmunemyastheniagravis(EAMG)(B6micereceived3timesofAChR/CFAimmunization)couldnotsignificantlyimprovetheclinicalsignsandclinicalscore.Whenthepossiblemechanismsweretested,wefoundthatCD3antibodytreatmentslightlydown-regulatedtheT-cellresponsetoAChR,modestlyup-regulationthemusclestrength.AndnosignificantdifferenceinthetitersofIgG2bwasfoundbetweenCD3antibodytreatedandcontrolgroups.ThesedataindicatedthatCD3-specificantibodywasnotsuitablefortreatingMG,anantibody-andcomplementmediatedautoimmunedisease,afterthisdiseasehasbeenestablished.TheroleofCD3-specificantibodyintreatingthiskindofdiseaseremainstobedetermined.
简介:FTY720,asphingosine1-phosphatereceptormodulator,inducesamarkeddecreaseinthenumberofperipheralbloodlymphocytesandexertsimmunomodulatingactivityinvariousexperimentalallograftandautoimmunediseasemodels.Inthisstudy,weevaluatedtheeffectofFTY720anditsactivemetabolite,(S)-enantiomerofFTY720-phosphate[(S)-FTY720-P]onexperimentalautoimmuneencephalomyelitis(EAE)inratsandmice.ProphylacticadministrationofFTY720at0.1to1mg/kgalmostcompletelypreventedthedevelopmentofEAE,andtherapeutictreatmentwithFTY720significantlyinhibitedtheprogressionofEAEandEAE-associatedhistologicalchangeinthespinalcordsofLEWratsinducedbyimmunizationwithmyelinbasicprotein.ConsistentwithratEAE,thedevelopmentofproteolipidprotein-inducedEAEinSJL/JmicewasalmostcompletelypreventedandinfiltrationofCD4+TcellsintospinalcordwasdecreasedbyprophylactictreatmentwithFTY720and(S)-FTY720-P.WhenFTY720or(S)-FTY720-PwasgivenafterestablishmentofEAEinSJL/Jmice,therelapseofEAEwasmarkedlyinhibitedascomparedwithinterferon-β,andtheareaofdemyelinationandtheinfiltrationofCD4+TcellsweredecreasedinspinalcordsofEAEmice.SimilartherapeuticeffectbyFTY720wasobtainedinmyelinoligodendrocyteglycoprotein-inducedEAEinC57BL/6mice.TheseresultsindicatethatFTY720exhibitsnotonlyaprophylacticbutalsoatherapeuticeffectonEAEinratsandmice,andthattheeffectofFTY720onEAEappearstobeduetoareductionoftheinfiltrationofmyelinantigen-specificCD4+Tcellsintotheinflammationsite.
简介:IL-33/ST2轴在几织物特定的自体免疫的疾病的致病被含有。腹的疾病(CD)是主要基因因素(HLA-DQ2/DQ8)和为危险性的etiologic(饮食的面筋)在被知道的唯一的自体免疫的疾病。我们测量了浆液层次和IL-33和它的受体的坚定的肠的织物表示在病人与的可溶的ST2与疾病活动调查他们的协会的CD。没有CD,IL-33和sST2的浆液和织物层次与在控制病人的那些相比在有CD的病人是显著地更高的。我们证明显著地从大麦和小麦麦胶蛋白质提取的有毒的肽从腹的病人在有教养的外部血mononuclear房间刺激IL-33和ST2的生产,强烈含有在CD的致病的IL-33/ST2轴。在织物和浆液的IL-33和它的受体ST2的高水平反映一个活跃煽动性的状态并且可以为疾病活动代表潜在的biomarker。IL-33/ST2版本,行动的模式,和规定的更好的理解将是关键的开发治疗学指向IL-33/ST2小径到对待CD。
简介:Xenogeneic胸腺移植能高效地在athymic接受者导致特定的有免疫力的忍耐到施主抗原。然而,许多裸体老鼠在xenogeneic胸腺移植以后患自体免疫的疾病(帮助)超过10个星期。CD4+CD25+Foxp3+规章的T(Treg)房间最近决心在在人和老鼠使忍耐有免疫力起一个枢轴的作用。因此,我们在受不了的老鼠帮助的猪胸腺接枝裸体的圆周调查了Treg房间的这subpopulation。我们的结果证明鼠标CD4+CD25+T房间和到CD4+T房间的CD4+CD25+Foxp3+Treg房间的比率上的Foxp3,CTLA-4和GITR的表达式显著地在受不了的鼠标帮助的猪胸腺接枝裸体的圆周被减少,与健康的猪或鼠标胸腺接枝裸体人鼠标相比。而且,在受不了的老鼠帮助的猪胸腺接枝裸体的老鼠CD4+CD25+T房间在xenogeneic与对应物相比在抑制免疫力的功能显示出更多的严重缺乏猪或syngeneic胸腺接枝裸体人老鼠没有帮助。因此,减少的频率,改变的显型和在猪胸腺接枝裸体人鼠标的鼠标CD4+CD25+Treg房间的功能的缺乏可以在这个模特儿贡献帮助的开发。
简介:热吃惊蛋白质90的提高的表示(HSP90)在全身的豺狼座erythematosus(SLE)的肾和浆液被发现了病人和MRL/Mp-Faslpr/Faslpr(MRL/lpr)自体免疫的老鼠。如果HSP90的抑制将在MRL/lpr老鼠减少疾病,我们调查了。在在vivo的vitro,有在IL-6的有免疫力刺激的显示出的减少的表示以前的HSP90禁止者Geldanamycin的mesangial房间的预告的处理,IL-12和号码,我们发现当与C57BL/6相比鼠标和MRL/lpr鼠标与HSP90禁止者17-DMAG对待时,HSP90表示在MRL/lpr肾被提高。与17-DMAG对待的MRL/lpr老鼠显示出减少的proteinuria并且减少了浆液anti-dsDNA抗体生产。Glomerulonephritis和glomerularIgG和C3没被17-DMAG的管理显著地在MRL/lpr影响。17-DMAG增加了CD8+T房间,减少的双negativeT房间,减少CD4/CD8比率和减少的小囊的B房间。这些研究建议HSP90可以在调整T房间区别和激活起一个作用并且HSP90抑制可以在豺狼座减少发炎。
简介:Graft-versus-host疾病(GVHD)是在造血的干细胞移植以后的最普通的复杂并发症。澄清像使用费的受体的角色4(TLR4),它是为细菌的lipopolysaccharides(LPS)的主要受体在尖锐GVHD的发展,我们使用了一个TLR4大美人(TLR4−/−)老鼠GVHD模型并且分析了内在的免疫学的机制。当TLR4−/−老鼠被用作骨头髓和splenocyte房间接枝施主或接受者时,GVHD症状出现和死亡被推迟与相比野类型(TLR4+/+)老鼠。另外,组织病理学说的分析在TLR4−/−BALB/c怪物,肝和小肠织物损坏与最小的淋巴球的渗入被减少。与TLR4+/+,TLR4−/−老鼠相对照,树枝状的房间没在处于一个不成熟的状态感应、留下的LPS期间表示CD80,CD86,CD40,MHC-II或IL-12。而且,TLR4−/−鼠标怒气的能力支持allogeneicT房间增长的树枝状的房间和,特别地T助手房间1(Th1)开发显然与TLR4+/+鼠标相比被稀释interferon-γ的树枝状的房间,和层次;(IFN-γ;)并且IL-10,Th2房间特定的cytokines,在TLR4−/−BALB/c比在TLR4+/+BALB/c妄想的老鼠。总的来说,我们的数据表明TLR4可以在GVHD和基因治疗可能提供的那指向的TLR4的致病起一个作用减少GVHD的风险的一条新处理途径。