冠状病毒Coronavirusl论文-2008 Generation of a Protective T-Cell Response Following Coronavirus Infection of the Central Nervous System Is Not Dep.pdf

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1、VIRALIMMUNOLOGYVolume21,Number2,2008©MaryAnnLiebert,Inc.Pp.173–187DOI:10.1089/vim.2008.0014GenerationofaProtectiveT-CellResponseFollowingCoronavirusInfectionoftheCentralNervousSystemIsNotDependentonIL-12/23SignalingKATHERINES.HELD,1WILLIAMG.GLASS,3YEVGENIYAI.ORLOVSKY,3KI

2、MBERLYA.SHAMBERGER,3TEDD.PETLEY,3PATRICKJ.BRANIGAN,3JILLM.CARTON,3HEENAS.BECK,3MARKR.CUNNINGHAM,3JACQUELINEM.BENSON,3andTHOMASE.LANE1,2ABSTRACTThefunctionalroleofIL-12andIL-23inhostdefenseanddiseasefollowingviralinfectionoftheCNSwasdetermined.Instillationofmousehepatitis

3、virus(MHV,apositive-strandRNAvirus)intotheCNSofmiceresultsinacuteencephalitisfollowedbyachronicimmune-mediateddemyelinat-ingdisease.Antibody-mediatedblockingofeitherIL-23(anti-IL-23p19)orIL-12andIL-23(anti-IL-12/23p40)signalingdidnotmuteT-celltraffickingintotheCNSorantiv

4、iraleffectorresponsesandmicewereabletocontrolviralreplicationwithinthebrain.Therapeuticadministrationofei-theranti-IL-23p19oranti-IL-12/23p40tomicewithviral-induceddemyelinationdidnotattenuateT-cellormacrophageinfiltrationintotheCNSnorimproveclinicaldiseaseordiminishwhit

5、emat-terdamage.Incontrast,treatmentofmicewithanti-IL-12/23p40oranti-IL-23p19resultedinin-hibitionoftheautoimmunemodelofdemyelination,experimentalautoimmuneencephalomyelitis(EAE).Thesedataindicatethat(1)IL-12andIL-23signalingaredispensableingeneratingapro-tectiveT-cellres

6、ponsefollowingCNSinfectionwithMHV,and(2)IL-12andIL-23donotcon-tributetodemyelinationinamodelindependentofautoimmuneT-cell–mediatedpathology.There-fore,therapeutictargetingofIL-12and/orIL-23forthetreatmentofautoimmunediseasesmayofferuniqueadvantagesbyreducingdiseaseseveri

7、tywithoutmutingprotectiveresponsesfollowingviralinfection.INTRODUCTION12R1chain(46).Moreover,signalingbythesecy-tokinesoftenelicitssimilarandoverlappingimmunere-INTERLEUKIN(IL-23)ANDIL-12AREHETERODIMERICsponses(45,46).Forexample,bothIL-12andIL-23arePROTEINSthatexhibitma

8、nysimilarstructuralaswellconsideredimportantinamplifyingT-cellresponsesin-asfunctionalproperties(45).Bo