1、中山大學博士學位論文Survivin和IL2重組痘苗病毒載體對樹突狀細胞功能的影響姓名：陶然申請學位級別：博士專業(yè)：生物化學和分子生物學指導教師：鄭利民20080606中山大學博十學位論文雙皋岡重組療曲病毒載體塒樹突狀細胞功能的影響ActivationofdendriticcellsbyrecombinantmodifiedvacciniavirusAnkaravectorsencodinghumanSurvivinandIL一2gen

2、esMajor：BiochemistryandmolecularbiologyPhDCandidate：RanTaoSupervisor：ProfessorLiminZhengAbstractRecombinantvacciniavirus(rVV)hasmanyadvantages：(i)largecapacitytoincorporateforeigngenes；(ii)highexpressionofrecombinantprot

3、einsinwiderangeofhostcells；(iii)effectiveinductionofbothhumoralandcellularimmuneresponsesTherefore，^ⅣWasregardedasasafeandpromisingvaccinevectorforcancerimmunotherapyTheattenuatedstrain“ModifiedvacciniavirusAnkara”(MVA)h

4、asattractedsignificantattentionasasafevaccinevectorusedtotransfertumorassociatedantigenDendriticcells(DCs)arethemostpotentprofessionalantigenpresentingcellsofthehumanimmunesystemwhichpossessanuniquecapacitytoactivatenaiv

5、eTcell、CD4ThandCD8CTLcellsAtpresent，thepreciseeffectofVVinfectiononDCfunctionisstilllargelyunknownHowever，severalstudieshaveshownthatVVinfectionalonecouldimpairthematurationandviabilityofDCs，whichwouldhampertheeffortstou

6、seVVasavectorfortumorimmunetherapyTherefore，theaimofthisstudyistosystemicallyinvestigatetheeffectofVVvectoronthedifferentiation，maturationandfunctionalactivitiesofhumanmonocytederiveddendriticcells，andtoexplorethepossibi

7、litytoovercometheintrinsicdefectofthisvectorbyincorporatinghumanSurvivinandIL2genesIna伊eementwithpreviousreports，wealsofoundthatDCsinfectedwithrMVAslightlyimpairtheirmaturationastestifiedbythereducedexpressionofCD83after

8、LPSstimulationHowevertheseinfectedDCsdoexpresshighlevelsoftargetgeneswitharetainedhighexpressionofcostimulatorymoleculesUponencounteringwithantogeneicTcells，theyCanefficientlystimulatetheTcellproliferationwithreducedapop