想

VOL.77,2003BCELLSANDANTIBODYPROTECTAGAINSTWNVINFECTION2585

detailedexperimentsarerequiredbeforeade nitiveconclu-sioncanbereachedregardingtheprotectiveroleofnaturalantibodiesagainstWNV.

Overall,ourdatasuggesttheimportanceoftheearlyanti-bodyresponseincontainingviremiaandlimitingdisseminatedinfectionofWNVintheCNS.TheseresultsareconsistentwiththoseofearlierstudiesthatshowedthattheabsenceofBandTcells(SCIDmice)butnotthatofTcellsalone(nudemice)intheBALB/cbackgroundincreasedmortalityassociatedwithWNVinfection(22).Nonetheless,itislikelythatotheraspectsoftheinnate(e.g.,interferonandNKcells)andadaptive(Tcells)immunesystemsalsohavecriticalrolesincontrollingWNVinfection.Indeed,preliminaryexperimentsinourlabo-ratorydemonstratedthatgeneticde cienciesofgammainter-feronorCD4 orCD8 TcellscauseincreasedmortalityinC57BL/6mice(M.Engle,B.Shrestha,andM.Diamond,un-publishedobservations).

ItisintriguingthatseverehumanWNVinfection,whichisheavilybiasedtowardanelderlypopulation,occursbecauseofadysfunctionalantibodyresponseagainstWNVearlyduringinfection;manyelderlypeoplehavedecreasedantibodypro-ductionandshorteneddurationsofprotectiveimmunityfol-lowingimmunization(39,51).Pharmacologicalinterventionwithantibodies,suchasimmuneimmunoglobulinorhuman-izedMAbs,mayprovideastrategyformitigatingCNSdiseaseinpatientswithWestNileencephalitis(38;Z.Shimoni,M.J.Niven,S.Pitlick,andS.Bulvik,Letter,Emerg.Infect.Dis.7:759,2001).

ACKNOWLEDGMENTS

andWeexperimentalR.thankBeatty,L.KramerE.Harris,andK.BernardforWNVisolatesandcelllinesandS.Virginadviceand/orS.reagents.Shresta,WeT.Chambers,thankD.Leib,andS.S.Schlesinger,VirginforControlTheworkmedicalandwasforcriticalPreventionsupportedreadingofthemanuscript.

(U50/CCU720545-02),bygrantsfromtheCentersforDiseaseNIH(T32Program,GM07067).

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