简介：T盒子抄写因素T赌注(Tbx21)作为类型1-like免疫的一个关键管理者出现了，起在在T和B淋巴细胞，以及树枝状的房间和自然漂亮房间的受动器房间命运的建立或维护的关键作用。几自体免疫的疾病，特别古典主义地与T助手1有关考虑的那些(Th1)免疫，看起来要求T赌注，至少是在老鼠模型判定了。这评论在autoimmunity在免疫，以及它的重要性总结T-bet的角色的当前的理解，与为治疗学的干预的含意。

简介：TcellhomeostasiscommonlyreferstothemaintenanceofrelativelystableTcellnumbersintheperipherallymphoidorgans.AmongthelargenumbersofTcellsintheperiphery,Tcellsexhibitstructuraldiversity,I.e.,theexpressionofadiverserepertoireofTcellreceptors(TCRs),andfunctionaldiversity,I.e.,thepresenceofTcellsatna(I)ve,effector,andmemorydevelopmentalstages.AlthoughthehomeostasisofTcellnumbershasbeenextensivelystudied,investigationofthemechanismsunderlyingthemaintenanceofstructuralandfunctionaldiversityofTcellsisstillatanearlystage.ThefundamentalfeaturethroughoutTcelldevelopmentistheinteractionbetweentheTCRandeitherselforforeignpeptidesinassociationwithMHCmolecules.Inthisreview,wepresentevidenceshowingthathomeostasisofTcellnumberanddiversityismediatedthroughcompetitionforlimitingresources.ThenumberofTcellsismaintainedthroughcompetitionforlimitingcytokines,whereasthediversityofTcellsismaintainedbycompetitionforself-peptide-MHCcomplexes.Inotherwords,diversityoftheself-peptiderepertoirelimitsthestructural(TCR)diversityofaTcellpopulation.Wespeculatethatcognatelowaffinityself-peptides,actingasweakagonistsandantagonists,regulatethehomeostasisofTcelldiversitywhereasnon-cognateornullpeptideswhichareextremelyabundantforanygivenTCR,maycontributetothehomeostasisofTcellnumberbyprovidingsurvivalsignals.Moreover,self-peptidesandcytokinesmayformspecializednichesfortheregulationofTcellhomeostasis.

简介：ImmunizationwithinactivatedautoreactiveTcells(Tcellvaccination)selectedfromindividual'sownTcellrepertoireprovidesauniqueinvivosettingfortestingimmuneregulationthatisknowntoinvolveinteractionsofavarietyofrelatedsurfacemolecules(1).ItinducesregulatoryimmuneresponsesthatcloselyresembletheinvivosituationwheretheimmunesystemischallengedbyclonalactivationandexpansionofgivenTcellpopulationsinvariousautoimmunediseases.TcellvaccinationprovidesapowerfulmeansofelicitingnaturalreactionsoftheimmunesysteminresponsetoclonalexpansionofTcells,whichcanusedasatherapeuticapproachtosuppressoreliminatespecificpathogenicautoreactiveTcellsinautoimmuneconditions.ClinicaltrialsusingTcellvaccinationtodepleteautoreactiveTcellsinhumanautoimmuneconditionshavebeguntorevealthepathologicrelevanceofvariousautoimmuneTcellpopulationsinthediseaseprocesses,providingauniqueopportunitytotesttheautoimmunetheoriesinaclinicalsetting.Cellular&MolecularImmunology.2004;1(5):321-327.

简介：T房间激活是在仅仅通过这个过程后来开始适应有免疫力的反应的一个批评过程特定的T房间区分进调停的武装受动器T房间的na(i)ve抗原实际有免疫力的response.DuringT房间激活，na(i)veT房间经历同种细胞的扩大并且获得能力杀死感染病原体的目标房间或生产为调整有免疫力的反应必要的cytokines。T房间的不恰当的激活或inactivation导致autoimmunity或严重免疫不全。PKC-有选择地在T房间被表示并且为调停要求了T房间激活过程。在PKC-缺乏的老鼠在T房间激活，幸存和activation-inducedcell死亡展出缺点。PKC-有选择地translocates到免疫学的触处并且调停为为T房间activation.Furthermore是必要的NF-B，AP1和NFAT的激活要求的信号，PKC--/-鼠标在vivo在T调停房间的有免疫力的回答的开发显示了多重缺点。PKC-因此是在vivo在T调停房间的有免疫力的回答在多重阶段调整T房间功能的一个批评分子。细胞与分子的免疫学。2006；3(4):263-270。

简介：Traditionally,thematerialswhichareregardedasantigensrecognizedbyγδTlymphocytesareproteinandcarbohydrate,notnucleicacidorlipid.Recently,ithasbeendemonstratedthatγδTcellscanrecognizelipidAanddirectlyinduceimmuneresponsesthatinvolveCD1(clusterofdifferentiationtype1)familyandTolllikereceptors(TLRs).Thisisareviewabouttheinteracting-mechanism,immunologicaleffectandclinicalapplicationofthem.Cellular&MolecularImmunology.

简介：Transplantrejection,liketolerance,isaTcell-dependentevent.ThereiscompellingevidencetosuggestthatinductionoftransplanttoleranceisanactivelylearnedprocessinwhichTcellsneedtoengagewiththealloantigensinordertolearntotoleratetheallograft.AfamilyofcytokineswhosereceptorsusethesameIL-2receptorγcchain(alsocalledthecommonγc)playsanimportantroleinregulatingmultipleaspectsoftheallograftresponse(I.e.Rejectionvs.Tolerance).ItisundeniablethatγccytokinescandriveclonalexpansionandeffectormaturationofalloreactiveTcells,andtherefore,targetingsuchcytokinesortheirreceptorcomponentsremainsanattractivewayofblockingtransplantrejection.However,wejuststartedtoappreciatethatγccytokinesalsoregulatetheacquisitionoftransplanttoleranceviaprogrammingactivatedTcellsforapoptoticcelldeathandviaguidingtheevolutionofregulatoryTcells.Thus,understandingpreciselytheroleofγccytokinesinregulatingTcellhomeostasisandTcellregulationiscriticallyimportantintheinductionoftransplanttolerance.

简介：Activation-inducedcelldeath(AICD),whichresultsfromtheinteractionbetweenFasandFasligand,isresponsibleformaintainingtolerancetoself-antigen.AdefectinAICDmayleadtodevelopmentofautoimmunity.Duringthelastseveralyears,muchprogresshasbeenmadeinunderstandingthemechanism(s)ofAICDanditspotentialroleinthepathogenesisofautoimmunediseases.Inthisreview,wesummarizethemostrecentprogressontheregulationofthesusceptibilityofTcellstoAICDanditspossibleinvolvementinautoimmunediseases.

简介：Itiswell-knownthatidiopathicthrombocytopenicpurpura(ITP)isanacquiredorgan-specificautoimmunehemorrhagicdiseaseanddysfunctionalcellularimmunityisconsideredimportantinthepathophysiologyofITP.However,polarizationpatternsandapoptosisprofilesofTlymphocytesremainunclear.Inthisstudy,weinvestigatedthepolarizationofTcellsubsets,theexpressionsofapoptoticproteinsFas/FasLonthesubsetsandthelevelofanti-apoptoticgenebcl-2andbaxmRNA.ItwasdemonstratedthattheratiosofTh1/Th2andTc1/Tc2inITPchildrenwereincreasedobviouslyandthattheaveragepercentageswereincreasedclearlyforTh1andTh2,butnotforTc1andTc2.InITPchildren,theenhancingexpressionsweredetectedforFasLonTh1andTc1andforFasonTh2andTc2.Withincreasinglevelofbcl-2mRNAanddecreasingexpressionofbaxmRNAinITPchildren,theratioofbcl-2/baxmRNAwasimprovedobviously,whichwaspositivecorrelatedwiththeratioofTh1/Th2.Takentogether,ourfindingsindicatethatITPisaTh1predominantdisease.ThispolarizationpatternofTcellsubsetsmightberelatedtothehighratioofbcl-2/baxmRNAandtheabnormalexpressionsofFasandFasLonTcellsubsets.Cellular&MolecularImmunology.

简介：IncreasedexpressionofFasbyhematopoieticprogenitorsinaplasticanemia(AA)suggeststhatFas/Fasligand(FasL)systemplaysakeyroleintheformationofseverepancytopenia.Tofurtherconfirmtheabovehypothesis,Tcellsfrom8patientswithAAweresystematicallystudiedfortheirFasL'sdistributionpattern,releasingmannerandproapoptoticactivity,comparedwithnormalrestingTcellsandartificiallyactivatedTcellblasts.TheresultsdemonstratedthatAATcellsabnormallyexpressedlowlevelsofmembrane-boundFasLandcontainedhighlevelsofintracellularFasLwhichcouldbetriggeredtoreleasebyhigh-dosephytohemagglutinin(PHA)pulse-stimulation.ThesupernatantsfromthePHA-stimulatedAATcellshadapparentcytotoxicityagainstFasL-sensitiveJurkatcells,whichcouldbesignificantlyinhibitedbymonoclonalantibodyagainstFasLinadose-dependentmanner,ornearlycompletelyabrogatedbyultracentrifugation.TheabovephenomenaalsoappearedonartificiallyactivatedTcellblasts,butthiswasnotthecaseonnormalrestingTcells.TheseresultsindicatethatAATcellisatypeof'preactivated'Tlymphocyte,characterizedbyoverexpressionofFasL,especiallyintracellularFasLwhichcanbestimulatedtoreleaseinbioavtiveexosomesboundform.Takentogether,ourdataprovidefurtheranddirectevidenceforthehypothesisthatTcellsmightmediatethedestructionofhematopieticprogenitorinAAthroughFas/FasLsystem.

简介：AccumulatingevidencehasdemonstratedthatregulatoryT(Treg)cellsplayanimportantroleinthemaintenanceofimmunologicself-toleranceandindown-regulatingvariousimmuneresponses.Thus,therehasrecentlybeenanincreasinginterestinstudyingthebiologyofTregcellsaswellastheirpotentialapplicationintreatingimmunediseases.ManytypesofTregcellsubsetshavebeenreportedinavarietyofdiseasemodels.Amongthesesubsets,αβ-TCR+CD3+CD4-CD8-doublenegative(DN)TregcellsaredefinedbytheircapabilityofinhibitingimmuneresponsesviadirectlykillingeffectorTcellsinanantigenspecificfashion.Furthermore,DNTregcellshavebeenshowntodevelopregulatoryactivityafterencounteringspecificantigens,partiallymediatedbytheacquisitionofMHC-peptidecomplexesfromantigenpresentingcells(APCs).ThepresentationofacquiredalloantigensonDNTcellsallowsforthespecificinteractionbetweenDNTregcellsandalloantigenreactiveeffectorTcells.OncetheDNTregandtargetcellshavecomeintocontact,killingisthenmediatedbyFas/Fas-ligandinteractions,andperhapsthroughotherunidentifiedpathways.Furthercharacterizationofthefunctions,molecularexpressionandmechanismsofactivationofDNTregcellswillhelpinthedevelopmentofnoveltherapiestoinduceantigenspecifictolerancetoselfandforeignantigens.Cellular&MolecularImmunology.2004;1(5):328-335.

简介：SKGmouse,asamodelofspontaneousrheumatoidarthritis(RA)bredrecentyears,issimilartothepatientswithRA.WeanalyzedtheclonotypesofTcellinfiltratingintojointsofSKGmiceininitialstageandlatestageofRAbyusingreversetranscriptase-polymerasechainreaction(RT-PCR)andsubsequentsingle-strandconformationpolymorphism(SSCP).TheresultsindicatedthatthepercentagesofclonotypesTCRVβ2andVβ8.2ofTcellcionotypesincreasedobviouslyto72.3%and60.2%,respectively.MicenumberwithidenticalTCRVβ2andVβ8.2clonotypesalsoclearlyincreasedinlatestageofdiseaseto100%and75%,respectively.TheseresultsmeanthatTcellswithTCRVβ2andVβ8.2clonotypesprobablyplayanimportantroleinRAprogressionofSKGmouse.SequencingoftheextractedDNAverifiedthatcommonbandsonSSCPgelwerederivedfromthesameTcellclonesamongsamplesfromdifferentjoints.TheresultsweobtainedimpliedthatRT-PCR/SSCPmethodwasasensitiveandcrediblemethodforanalyzingTcellclonotypes.WhentheTcellsofSKGmousewereadoptivelytransferredtoanudemouse,itwasverifiedthattheTcellsinfiltratingintojointswererelatedtomorbidformationofRA.

简介：Thec-JunN-terminalkinases(JNKs)areclassicstress-activatedproteinkinases.ManycellularstresseshavebeenshowntostimulateJNKactivation.Inthisreview,wefocusonribotoxicstressesbasedontheirmultiplebiologicalpotenciesincludinganti-HIV-1activity.Someofthefunctionsofribotoxinsandthesignalingtransductionpathwaythatmediatedarementioned.Differentfromotherstimulators,ribotoxicstressesactonspecialmotifsof28SrRNAintranslationallyactivemammalribosomes.BindinganddamagingonthemotifleadstoJNKactivationandsubsequentlybiologicalresponsetothesignalinitiator,whichisnamedribotoxicstressresponse.

简介：interleukin-24(IL-24)能在人的癌症的一个大系列导致apoptosis，是记录得好的MDA-7/IL-24基因的导出的房间线，而是效果在未知的老鼠黑瘤房间遗体上转。IL-24(pEGFP-IL-24)的真核细胞的表示plasmid被DNA再结合技术构造。再结合plasmid和空向量是进B16F0房间的transfected，IL-24的表情被LSM决定，B16F0房间的增长被MTT试金，和apoptosis率测量，B16F0房间的房间周期分发被FCM测量。在老鼠固体肿瘤的IL-24基因transfection的禁止的效果被观察并且测量。与控制相比，B16F0房间的增长被transfection与pEGFP-IL-24禁止，transfected房间的G2/M阶段也是increased.Moreover，在与pEGFP-IL-24与B16F0房间transfected接种以后，有可检测的肿瘤的鼠标的百分比被减少。在老鼠模型的肿瘤的生长率显著地与控制相比在IL-24基因治疗组被禁止。B16F0细胞的增长被pEGFP-IL-24的pEGFP-IL-24transfection.Theintratumor注射禁止能显著地在老鼠禁止稳固的肿瘤的生长。

简介：Themainapproachtoreducegraftrejectionhasbeenfocusedonthedevelopmentofimmunosuppressiveagentsatpresent.Althoughthesestrategieshavereportedlyreducedgraftrejection,therehasbeenareciprocalincreaseinmoresevereimmunosuppressionandlethalinfections,aswellasseveresideeffects.BlockadeofcostimulatoryTcellresponsehasbeenprovedasoneofusefulstrategiestoreducegraftrejection.Furthermore,ithasbeenshownthatinfusionofdendriticcells(DCs)withapotentnegativeregulatoryabilityforTcellscouldprolongallograftsurvival.InthisstudymouseDCs(mDCs)weretransfectedwiththerecombinantplasmidpcDNA3.0containingmouseinduciblecostimulator-Ig(mICOS-Ig)cDNAbyelectroporation.ThetransientexpressionofmICOS-IginmDCcouldbedetectedbyELISAandSDS-PAGE.MouseICOS-IgfusionproteinexpressedinmDCandmICOS-Iggene-modifiedmDCcouldinhibitlymphocyteproliferationinmixedlymphocyteculture(MLC)invitro.Furthermore,mICOS-Iggene-modifiedmDCcouldinhibitlymphocyteproliferationinrecipientmice.TheseresultssuggestedthatmICOS-Iggene-modifiedmDCexertedinhibitoryeffectsonTcells,andmightbesuitablefortreatmentorpreventionofgraftrejectionandimmunopathologicdiseases.

简介：ToelucidatethestructuresofSLA-DR(swineleukocyteantigenDR)genesofthreeChinesepigstrains(Gz,BmandYn),theSLA-DRAandSLA-DRBcDNAwereamplifiedbyRT-PCRandsubjectedtodeterminethesequences.ThewholestructuresofSLA-DRAallelesareidenticalamongthreestrains,consistingof759nucleotidesincludinganopenreadingframe(ORF),andaresharedwiththosereportedfromNIHminipigsSLA-DRAcandSLA-DRAd.ThesamelengthoftheORF-containingSLA-DRBgenesofthreeChinesepigstrainswasalsoidentified.Theyarecomposedof801nucleotidesencodingaxenogeneicantigenmoleculeof266aminoacidresidues.ThenucleotidesequencesoftheSLA-DRBgenes,however,aredifferentwhencomparedeitheramongthethreestrainsorwiththepublisheddataofSLA-DRBsequences,whichallowedournovelSLA-DRBallelesreceivingtheiraccessionnumbersAY102479,AY102480andAY102481fromtheGenBank.ThisstudyfurtherrevealsthatthephylogenichomologiesofMHCDRorDR-likegenesinstructuresofnucleotidesanddeducedaminoacidsbetweenChinesepigs(SLA)andhuman(HLA-DRB1*0901)arebetterthanthosebetweenpigsandmice(H-2bEβ).HighsimilaritieswerealsofoundforDRα-DRβheterodimersbetweenChinesepigsandhumanintermsofaminoacidssequencescriticalforbindingwithhumanCD4coreceptormolecule,whicharebetterthanthosebetweenSLA-DRandH-2I-Emolecules.Afunctionaltestindicatedthat,bycotransfectionwithBm-DRAandBm-DRBgenes,theBm-DRmolecule-expressedL929cellscouldstimulatehumanTcellsquitewellinaxenogeneicreactioninpresenceofhumanAPCs.

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：Interleukin-12(IL-12)isacriticalcytokinerepresentingthelinkbetweenthecellularandhumoralbranchesofhostimmunedefenseapparatus.IL-12-inducedcytotoxiclymphocyte(CTL)developmentisacentralmechanisminimmuneresponsesagainstintracellularinfectiousagentsaswellasmalignantgrowth.However,themolecularbasisoftumor-specificCTLresponsesmediatedbyIL-12remainspoorlydefined.Inthisstudy,weaddressedthisissueinacomprehensivemannertoprobeintoIL-12-inducedanti-tumorresponsesbyglobalgeneexpressionprofilingofmRNAexpressioninCD8+TcellsinatransplantablesyngeneicmousemammarycarcinomamodeltreatedornotwithrecombinantIL-12.AstrongtumorregressionwasinducedbytheIL-12treatment.AnintrospectionofdifferentialgeneexpressionatanearlystageoftheIL-12-initiatedCTLactivationrevealsinterestinggenesandmolecularpathwaysthatmayaccountforthemarkedtumorregression,andislikelytoprovidearichsourceofpotentialtargetsforfurtherresearchanddevelopmentofeffectivetherapeuticmodalities.Cellular&MolecularImmunology.2004;1(5):357-366.

简介：Directintratumoralintroductionoftherapeuticorregulatorygenesisadevelopingtechnologywithpotentialapplicationforcancergenetherapy.Macrophageinflammatoryprotein-1beta(MIP-1β)isachemokinewhichcanchemoattractimmunecellssuchasTcells.Inthepresentstudy,murinecolorectaladenocarcinomaCT26cellsweretransfectedwitharecombinantadenovirus(AdhMIP-1β)carryingthehumanMIP-1βgene.24hpost-transfection,hMIP-1βlevelsreachedapproximately980pg/mlinsupernatantsof106hMIP-1β-transfectedCT26cells.Moreover,thesupernatantsexhibitedchemotacticactivityforCD8+Tcells,CD4+Tcells,NKcellsandimmatureDCs.IntratumoralinjectionofAdhMIP-1βsignificantlyinhibitedtumorgrowthandprolongedthesurvivaltimeoftumor-bearingmice.IntratumoralhMIP-1βgenetransferalsoinducedpowerfultumor-specificCTLresponsesinvivo.ThetherapeuticeffectsofhMIP-1βgenetherapyweregreatlyreducedfollowinginvivodepletionofbothCD4+andCD8+Tcells,butwereunaffectedbydepletionofsingleTcellsubsets.ImmunecelldepletionexperimentsalsorevealedthatNKcellsplayedanimportantroleinhMIP-1β-inducedantitumorresponses.TheseresultssuggestthatintratumoralexpressionofhMIP-1βhasthepotentialeffecttoinducehostantitumorimmunityandmayprovetobeausefulformofcancergenetherapy.

简介：在维持平衡外部有免疫力的system.Recent的一个重要角色学习的CD4+CD25+规章的T(TR)房间玩证明了TR房间可以也在压制反肿瘤免疫者反应起一个关键作用。以便调查TR极化上的肿瘤免疫者微型环境和它的影响，糟糕产生免疫性的肿瘤房间线D5(C57BL/6，H-2b)，产生免疫性的肿瘤房间线FBL3(C57BL/6，H-2b)并且H22BALB/c，H-2d)被用来建立syngeneic/allogeneic，糟糕产生免疫性/产生免疫性的混合淋巴细胞肿瘤房间文化(MLTC)。我们的结果表明在告知的splenocytes与D5肿瘤房间刺激了的syngeneic的MLTC的CD4+CD25+T房间的比例与H22房间比那高(0.43%对0.044%，并且类似的结果在与.Thesplenocytes从更高表明的房间比从D5肿瘤的allogeneicMLTC，房间，和splenocytes刺激了机智的CD4+CD25+房间分配的D5肿瘤的syngeneicMLTC与上层清液刺激了的D5肿瘤房间(0.39%对0.04%)刺激的allogeneicsplenocytes出现了TGF-1和Th2面向的cytokines(IL-4和IL-10)在糟糕产生免疫性的肿瘤房间的syngeneicMLTC的上层清液被统治。我们的结果为学习位于肿瘤免疫者监视下面的机制以及为肿瘤免疫疗法提供了有用信息。

简介：生来的杀手(NK)房间是骨头导出髓的淋巴细胞。他们生产cytokines调整获得的免疫的发展。鉴于他们在母亲胎儿的接口的累积，子宫的生来的杀手(uNK)房间也被认为在怀孕期间起必要作用。我们的结果在子宫的子宫内膜，肝，怒气和外部血由NK房间比较了cytokine分泌物侧面的差别，并且由uNK房间集中了于cytokines分泌物。在怀孕鼠标的子宫的子宫内膜的IFN-和TNF-的表达式是比在肝的那些低的，这被表明，但是他们在怀孕期间显著地增加。我们的学习证明uNK房间的数字在怀孕期间显著地被增加。他们比另外的导出器官的NK房间，和他们也分泌IL-4和IL-5的次要的数量的生产了更多的IFN-和TNF-。结果显示uNK房间生产的IFN-和TNF-保证了成功的怀孕进步。