冠狀病毒Coronavirusl論文-1988 Coronavirus-JHM-Induced Demyelinating Encephalomyelitis in Rats _ Analysis of the Intrathecal Immune Response.pdf

冠狀病毒Coronavirusl論文-1988 Coronavirus-JHM-Induced Demyelinating Encephalomyelitis in Rats _ Analysis of the Intrathecal Immune Response.pdf

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1、Coronavirus-JHM-InducedDemyelinatingEncephalomyelitisinRatsAnalysisoftheIntrathecalImmuneResponseR.DORRIES,S.SCHWENDER,H.WEGE,H.HARMS,R.WATANABE.ANDV.TERMEULENInstitutfurVirologieundImmunbiologiederUniversitat0-8700Wurzburg,FRGAclinicallyrelevant,subacute,demyelinatingencephalom

2、yelitiscanbeinducedinLewisratsbyintracerebralinfectionwiththemurinecoronavirusJHM.Thediseaseischaracterizedbyhindlegparesis,ataxicgait,anddecreasedweightgain.Histo-pathologically,areasofprimarydemyelinationaredetectableinbrainandspinalcord,infiltratedbymononuclearcells,andinclos

3、eassociationwithperivascularcuffsoflymphoidcells.'Severalobservationsinrecentyearssupporttheideathatbesidesthegeneticbackgroundofthehostandvirus,theimmunesystemseemstoplayacrucialroleinthecourseofthedisease.Asweshowed,'thetransferofbasicmyelinprotein(BMP)-specificT-celllines,gen

4、eratedfromSDE-diseasedLewisrats,causesperivas-cularcuffinginhealthyrecipients,indicatingautosensitizationtobrainantigens.Pre-sentationofautoantigensmaybeassociatedwiththeinductionofclassI1antigensonratastrocytesbyJHMvirus,asshownininvitrostudies?BecauseSDE-diseasedanimalsreveala

5、clonallyveryrestrictedJHM-specificantibodyresponsewithalowtiterinthecentralnervoussystem:inductionofIaantigensonastrocytesbyvirusparticlesthathaveescapedneutralizationislikelytohappeninvivoaswell.Fromthesedata,wewantedtodeterminethedistributionoflymphocytesubsetsinthebrainofSDE-

6、diseasedLewisratsinrelationtovirus-infectedcellsandforthebraincelltypeinfectedinoraroundademyelinatedarearevealingintenselymphocyteinfiltra-tion.Byacombinationofcomputer-aidedcytophotometryandimmunocytochemistryamulticoloredtopographicmapofarepresentativedemyelinatedareainthecer

7、ebellumofanSDEanimalwasdeveloped,revealingthefollowingpicture:Adjacenttoaperivascularcuff,cytotoxicTcellsdistributefromthecenterofthefocaldemyelination,almostfreeofvirus-infectedcellsversustheabundantlyinfectedmarginalzone.TherimoftheplaqueisthesitewhereinfiltratingT-helpercells

8、aredetectedincloseassociationwithBlymphocytesan

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