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：ＴＣＥＬＬＲＥＣＥＰＴＯＲＧＥＮＥＲＥＡＲＲＡＮＧＥＭＥＮＴＡＮＡＬＹＳＩＳＩＮＴＨＥＰＲＩＭＡＲＹＣＵＴＡＮＥＯＵＳＴＣＥＬＬＬＹＭＰＨＯＭＡＱｉｕＢｉｎｇｓｅｎ邱丙森ＷａｎｇＰｉｎｇ１王平ＧａｏＨｏｎｇｙａｎｇ２高红阳ＳｈａｎｇＹｉｆｅｉ２...

简介：T房间受体(TCR)的结扎独自是不够的导致T淋巴细胞的完整的激活。介绍房间(APC)和T房间的抗原上的另外的ligand受体相互作用(costimulation)被要求。T房间costimulation被显示了为得到有效T房间回答必要，包含在T房间开发期间的所有阶段。然而，costimulation由影响T房间的功能的机制仍然需要被阐明。在最近的年里，在癌症，传染疾病以及自体免疫的疾病作为潜在的治疗在costimulation的研究被献殷勤。在这评论，我们讨论了调整T房间增长，房间周期前进，cytokine生产，幸存，和存储器开发的细胞内部的costimulation信号。一般来说，phosphoinositide-3kinase(PI3K)的小径/proteinkinaseB(PKB，也作为Akt知道)/nuclear因素B(NF-B)可能对许多costimulatory效果中央。通过这些小径，costimulation由survivin和曙光B表示的维护控制T房间扩大和增长，并且由调整bcl-2家庭成员的表达式支撑长期的T房间幸存和存储器开发。

简介：MicroRNAs(miRNAs)aresmall,non-codingsingle-strandedRNAsthatcanmodulatetargetgeneexpressionatposttranscriptionallevelandparticipateincellproliferation,differentiation,andapoptosis.Tcellshaveimportantfunctionsinacquiredimmuneresponse;miRNAsregulatethisimmuneresponsebytargetingthemRNAsofgenesinvolvedinTcelldevelopment,proliferation,differentiation,andfunction.Forinstance,miR-181familymembersfunctioninprogressionbytargetingBcl2andCD69,amongothers.MiR-17tomiR-92clustersfunctionbybindingtoCREB1,PTEN,andBim.ConsideringthatthesuppressionofTcell-mediatedimmuneresponsesagainsttumorcellsisinvolvedincancerprogression,weshouldinvestigatethemechanismbywhichmiRNAregulatesTcellstodevelopnewapproachesforcancertreatment.

简介：Tostudytheroleofnaturalkiller(NK)cellsinTcellrecruitmentinmurineliverinfectedwithvirus,micewereintravenouslyinjecteddailywithanti-NK1.1^+antibodytodepleteNKcells.Lymphocytesinthelivertissueofmiceinfectedwithtype5adenovirusdepletedintheE1andE3regionswereassessedbyfluorometricactivatedcellsorting(FACS).Ex-pressionofchemokineIP-10anditsreceptorCXCR3mRNAintheliver,hepaticlymphocytesandspleentissuewereexaminedbyreversetranscriptionpolymerasechainreaction(RT-PCR).Serumalmfineaminotransferase(ALT)wasmeasuredasanindicatorofliverinjury.Itwasfoundthatinfectionofadenovimsandanfi-Fasmonoclonalantibody(mAb)intomicecausedliverinjuryandhighexpressionofinterfemn-γinducibleprotein-10(IP-10)mRNAintheliver.Anfi-NK1.1^+mAb,whichwasintraperitoneallyinjectedintothemiceinfectedwithadenovirus,suppressesTcellrecruitmentandexpressionofIP-10mRNAinthehver.Slighterhverinjurywasalsoobserved.Afterviresinfection,expressionofCXCR3mRNAinspleenandhvertissuewasobservedatdifferenttime.TheresultssuggestedthatTcellrecruitmentwasinitiatedbyNKcelldependentchemokineIP-10,whichinducedactivatedTcellspriminginthespleentothehverofthemouse.NKcellsplayedakeyroleinTcellrecruitmentintheliverofmouseinfectedwithadenovims.

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

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

简介：Inthepresentstudy,theeffectofelectroacupuncture(EA)onimmunesystemwasobservedintheratbyusingmicro-wholeblooddirectimmunofluoreseenceStainingassaytodetectchangesoftheperipheralbloodTlymphocytesubgroupandemployingredbloodcell(RBC)C3breceptor-yeastrosettetestandredbloodcell-ICrosettetesttoanalyzeerythroeyticimmunefunction.ResultsshowedthatafterEAof“Zusanli”(ST36),CD4^+,RBC-C3bRRandRBC-ICRintheperipheralbloodofthenormalratsincreasedsignificantlywhileCD8^+hadnoanyconsiderablechangesandapositivecorrelationbetweenCD4+andRBC-C3bRRwasfound.Inimmuoosuppressionmodelrats,thevaluesofCD4^+andRBC-C3bRRwereobviouslylowerthanthoseofthenormalcontrolgroupwhileCD8^+hadnoanystrikingchanges;butafterEAtreatment,therewerenoevidentdifferencesbetweenEAgroupandnormalcontrolgroupintheabove-mentionedindexes.Therewerealsonoanysignificantdifferencesbetweennon-acupointgroupandnormalcontrolgroupinthoseindexes.ResultssuggestthatEAof“Zusanli”(ST36)canraiseTcellimmunefunctionandRBCadhesionfunctioninbothnormalratsandimmunosuppressionmodelrats,bothofwhichpresentapositivecorrelation.

简介：AbstractObjective:To analyze the proportion of peripheral regulatory T cells (Tregs) and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain (TIGIT) and CD226 on Tregs in patients with recurrent spontaneous abortion (RSA).Methods:The proportion of CD3+CD4+CD25+Foxp3+ Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.Results:The proportion of Tregs in the RSA group (4.41 % ± 1.54%) was significantly lower than that in the control group (5.27% ± 1.52%, P = 0.0374). Compared with the normal pregnant women, patients with RSA showed decreased TIGIT expression (54.75 ± 9.70% vs. 63.07 ± 12.48%, P = 0.0066) and increased CD226 expression on Tregs (25.59% ± 8.22% vs. 20.46% ± 6.97%, P = 0.0168). The ratio of CD226 to TIGIT in the RSA group (0.48 ± 0.19) was higher than that in the control group (0.34 ± 0.15, P = 0.0027). The proportion of TIGIT+CD226+ Tregs was significantly lower in patients with RSA (9.30% ± 4.95% vs. 13.43% ± 4.72%, P = 0.0020) than in the controls.Conclusions:Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.

简介：Thecurrentconceptof“AdoptiveTCellImmunotherapyofCancer”isquitedifferentfromhowitwasoriginallyconceived．Withthedevelopmentofmoderntechnologyinmolecularbiology,cellbiology，immunologyandbiochemistryduringthelasttwentyyearsorso，adoptiveimmunotherapyhasgrownfromitsinitialformofasimple“bloodcelltransfer”intoitspresentprocesswhichinvolveshostvauccination，effectorcellactivation／polarizationandgeneticmodification．Withtheuseofimmuneadjuvantsandtheidentification／characterizationoftumor-reactiveTcellsubsets，orincombinationwithothertherapeuticstrategies，adoptivelytransferredTcellshavebecomemuchmorepotentinmediatingtumorregression．Inaddition，studiesonthetraffickingofinfusedTcells，celltransferperformedinlymphopenicmodels，aswellasthediscoveryofnoveltechniquesinimmunemonitoringforthegenerationofeffectorcellsinvitroandaftercelltransferinvivohaveprovidedusefultoolstofurtherimprovethetherapeuticefficacyofthisapproach．ThisarticlewillreviewtheserelatedaspectsofadoptiveTcellimmunotherapyofcancerwithspecificcommentsoncertaincriticalareasintheapplicationofthisapproach．Withtherapidlyevolvingadvancesinthisarea，itishopedthatthiscellularimmunologictherapyasitwasconceptualizedinthepast，canbecomemoreusefulinthetreatmentofhumancancerinthenearfuture．

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.

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简介：AbstractCD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy is effective in refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL). This review focuses on achievements, current obstacles, and future directions in CAR-T research. A high complete remission rate of 68% to 93% could be achieved after anti-CD19 CAR-T treatment for B-ALL. Cytokine release syndrome and CAR-T-related neurotoxicity could be managed. In view of difficulties collecting autologous lymphocytes, universal CAR-T is a direction to explore. Regarding the high relapse rate after anti-CD19 CAR-T therapy, the main solutions have been developing new targets including CD22 CAR-T, or CD19/CD22 dual CAR-T. Additionally, some studies showed that bridging into transplant post-CAR-T could improve leukemia-free survival. Some patients who did not respond to CAR-T therapy were found to have an abnormal conformation of the CD19 exon or trogocytosis. Anti-CD19 CAR-T therapy for R/R B-ALL is effective. From individual to universal CAR-T, from one target to multi-targets, CAR-T-cell has a chance to be off the shelf in the future.

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简介：CD8+T房间在对感染向保护提供细胞内部的病原体和一些肿瘤起一个枢轴的作用，这很好被接受。在许多情况中，保护的免疫为时间(免疫学的记忆)的长经期被维持。在过去的年，不得不以便完成这些多重任务，受动器的不同子集和记忆T房间被产生，变得明显。然而，直到今天，很少对子集区别并且预定系命运决定的内在的机制被知道。在这上下文，在哪个功能的同种细胞的扩大和phenotypical异质的水平被完成决定具有特殊重要性。为T房间子集多样化的不同模型被建议了；这些在priming和同种细胞的扩大期间主要在时间点不同(优先，在期间，或在第一个房间部门以外)区别什么时候编程序，被导致。最近发达的单个房间的采纳转移技术允许我们证明那个单个先锋房间仍然忍受完整的粘性开发不同T房间子集进过多。这观察指向向在第一个房间部门以外仍然是起作用的因素塑造T房间子集区别。这些调查结果为疫苗的开发有重要含意，，向不同子集的区别模式的调整能成为强大的策略提高疫苗的功效和质量。

简介：AbstractAdult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.

简介：AbstractRespiratory viruses are major human pathogens that cause approximately 200 million pneumonia cases annually and induce various comorbidities with chronic obstructive pulmonary disease (COPD), resulting in significant health concerns and economic burdens. Clinical manifestations in respiratory viral infections and inflammations vary from asymptomatic, mild, to severe, depending on host immune cell responses to pathogens and interactions with airway epithelia. We critically review the activation, effector, and regulation of T cells in respiratory virus infections and chronic inflammations associated with COPD. Crosstalk among T cells, innate immune cells, and airway epithelial cells is discussed as essential parts of pathogenesis and protection in viral infections and COPD. We emphasize the specificity of peptide antigens and the functional heterogeneity of conventional CD4+ and CD8+ T cells to shed some light on potential cellular and molecular candidates for the future development of therapeutics and intervention against respiratory viral infections and inflammations.

简介：ObjectiveToinvestigateTcellactivationfollowingfacialnerveaxotomizationandlatentneuroimmunologicmechanismsintraumaticfacialparalysis.MethodsAmurinemodeloffacialnervetransactionwasused.LymphocytesfromcervicalandmesentericlymphnodesinBABL/cmiceatspecifictimeswerecollectedandexpressionratesofCD69onTcellswereassessedbyflowcytometry.ResultsInfiltratingTcellsweredetectedaroundthefacialneuronsinthefacialnervenucleusinmicewhosefacialnervewastransected.ImmunofluorescentstainingshowedrecruitmentofactivatedTcells.Threedayspost-facialnervetransection,theexpressionrateofCD69onTcellsfromcervicaldraininglymphoidnodes(CDLNs)wassignificantlydifferentfromthatonTcellsfrommesentericlymphnodes(MLNs)(P=0.0457),whereasthelatterwassimilartothatinanimalsundergoingshamsurgeriesandthatinblankcontrolanimals(p=0.2817and0.2724,respectively).Twoweekspost-nervetransection,theTcellCD69expressionratefromCDLNsremainedatahigherlevelandthanthatinthesham-operationanimals(p=0.0007).Attwoweeks,CD69expressionrateonTcellsfromMLNswasalsoup-regulatedanddifferentcomparedwiththesham-operationanimalsandwithitselfatthreedayspost-operation(p=0.0082and0.0133,respectively).ConclusionTcellsappeartobeactivatedandup-regulatedinCDLNsfollowingfacialnervetransection.ThereisevenevidenceofTcellactivationinMLNsat2weekspost-nervetransection.Thissuggestesanalterationofimmuneresponsefromlocaltogeneralimmunityintheacutestageoffacialnervetrauma,whichmayhelpcoordinatingandcontrollingthescalesandorientationoftheneuroimmuneresponseduringthepathogenesisandprogressionoffacialnervetrauma.

简介：TheaimofthisstudyistofindtheexperimentalevidencethattheprecursorfrequencyofalloreactiveCTLsisproportionaltothenumberoftheT-cellepitopespecificities.ThenumberofT-cellepitopespecificitieswasmanipulatedbypulsingdifferentnumberofHLA-A2restrictedpeptide(s)ontotheT2cells,whichactedasstimulatingcellstoelicitallo-reactionbyco-culturingwithperipheralbloodlymphocytes(PBLs)ofHLA-A2negativeindividual.TenHLA-A2restrictedpeptides(allwerenormalcellcomponents)weresynthesized,andcellpeptideextractwaspreparedbyfrozenandthawed.T2cellsloadedwithdifferentnumberofpeptide(s)wereco-culturedwithPBLsofanHLA-A2negativeindividual;thelatterwerestainedwithPKH67inadvance.Thentheproliferationwasmonitoredwithflowcytometry,andtheprecursorfrequencyoftheeffectorcellswasanalyzedbytheModFitSoftware.After6dofculture,noproliferationwasobservedinthebulkcultureofPBLalone,andobviousproliferationtookplacewhenPBLsoftheHLA-A2negativewereco-culturedwithT2cellsloadedwithorwithoutloadingpeptide(s).TheprecursorfrequencyofthealloreactiveCTLswas0.052819forco-culturewithT2cellsloadedwithoutpeptide;howeveritwas0.030429forT2cellswithEBV/LMP2Aand0.030528forT2cellsloadedwithasingleautogeneicpeptide,andincreasedupto0.144942forT2cellsloadedwith10autogeneicpeptides;theprecursorfrequencywas0.203649whenco-culturedwithT2cellsloadedwithmiscellaneouspeptidesextractedfromthecytoplasmofT2cells.ThisstudyrevealsthattheprecursorfrequencyofalloreactiveCTLsisproportionaltothenumberofT-cellepitopespecificities,andindependentofthedensityoftheallogeneicHLAClassⅠmolecule.OurfindingssupportthehypothesisthatthealloreactiveTcellpopulationscomprisemiscellaneousTcellclones;eachisspecifictocorrespondingpMHC.ThenovelconstellationofpeptidespresentedbyallogeneicMHCmoleculesmakesthous