CD28B7信号在再生障碍性贫血T淋巴细胞异常活化中的作用的开题报告.docxVIP

CD28B7信号在再生障碍性贫血T淋巴细胞异常活化中的作用的开题报告

Introduction:

RefractoryAnemia(RA)isatypeofmyelodysplasticsyndrome(MDS)whichischaracterizedbyinadequateproductionofmaturebloodcellsleadingtoanemia.AbnormalactivationofTlymphocyteshasbeenproposedasoneofthemechanismsofRA.TlymphocytesareactivatedbyinteractionbetweenT-cell-specificantigenreceptor(TCR)andantigenpresentedbymajorhistocompatibilitycomplex(MHC)onantigen-presentingcells(APC).CostimulatoryreceptorslikeCD28onTcellsandCD80/CD86onAPCprovidesecondaryactivationsignalsrequiredfortheactivationofTcells.TheCD28-CD80/CD86interactionhasbeenimplicatedinthepathogenesisofvariousautoimmunediseases.Inthisstudy,weaimtoinvestigatetheroleofCD28-CD80/CD86signalingintheabnormalactivationofTlymphocytesinRA.

Hypothesis:

CD28-CD80/CD86signalingcontributestoabnormalactivationofTlymphocytesinRA,leadingtotheproductionofinflammatorycytokinesandultimatelycausingbonemarrowfailure.

Objectives:

1.ToassesstheexpressionofCD28anditsligands(CD80/CD86)onTcellsandAPCs,respectively,inRApatients.

2.ToevaluatetheeffectofCD28-CD80/CD86signalingonT-cellactivationandtheproductionofinflammatorycytokinesinRApatients.

3.ToinvestigatethemechanismbywhichCD28-CD80/CD86signalingleadstoabnormalT-cellactivationinRApatients.

Methodology:

1.Patients:Wewillinclude20RApatientsand20healthycontrols.TheRApatientswillbediagnosedbasedontheWorldHealthOrganizationcriteria.

2.IsolationofTcellsandAPCs:CD4+Tcellswillbeisolatedfromperipheralbloodmononuclearcells(PBMCs)usingamagneticbeadseparationtechnique.APCswillbeisolatedfromPBMCsbyadherencetoplastic.

3.Flowcytometry:TheexpressionofCD28anditsligands(CD80/CD86)willbeassessedonTcellsandAPCs,respectively,byflowcytometry.

4.Activationassays:CD4+Tcellswillbestimulatedw