Ribavirin Exerts Differential Effects on Functions of Cd4+ Th1, Th2, and Regulatory T Cell Clones in Hepatitis C 英文参考文献.docVIP
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RibavirinExertsDifferentialEffectsonFunctionsofCd4Th1,Th2,andRegulatoryTCellClonesinHepatitisC英文参考文献
RibavirinExertsDifferentialEffectsonFunctionsofCd4+
Th1,Th2,andRegulatoryTCellClonesinHepatitisC
BettinaLanghans*,HansDieterNischalke,SimoneArndt,IngridBraunschweiger,JacobNattermann,
TilmanSauerbruch,UlrichSpengler
DepartmentofInternalMedicineI,UniversityofBonn,Bonn,Germany
Abstract
Ribavirin improves outcomes of therapy in chronic hepatitis C but its mode of action has still remained unclear. Since
ribavirinhasbeenproposedtomodulatethehost’sTcellresponses,westudieditsdirecteffectsonCD4 Tcellcloneswith
+
diverse functional polarization which had been generated from patients with chronic hepatitis C. We analysed in vitro
proliferation([3H]thymidineuptake)andcytokineresponses(IL-10,IFN-gamma)atvaryingconcentrationsofribavirin(0–
+
10mg/ml)in8,9and7CD4 TH1,TH2andregulatoryTcell(Treg)clones,respectively.Inco-cultureexperiments,wefurther
determinedeffectsofribarivinoninhibitionofTH1andTH2effectorcellsbyTregclones.Allcloneshadbeengenerated
from peripheral blood of patients with chronic hepatitis C in the presence of HCV core protein. Ribavirin enhanced
proliferationofTeffectorcellsandincreasedproductionofIFN-gammainTH1clones,buthadonlylittleeffectonIL-10
secretion in TH2 clones. However, ribavirinmarkedly inhibited IL-10 release in Treg clones in adose dependentfashion.
TheseTregclonessuppressedproliferationofTeffectorclonesbytheirIL-10secretion,andinco-cultureassaysribavirin
reversedTreg-mediatedsuppressionofTeffectorcells.Ourinvitrodatasuggestthat-inadditiontoitsimmunostimulatory
effectsonTH1cells-ribavirincaninhibitfunctionsofHCV-specificTregsandthusreversesTreg-mediatedsuppressionofT
effectorcellsinchronichepatitisC.
Citation:LanghansB,NischalkeHD,ArndtS,BraunschweigerI,NattermannJ,etal.(2012)RibavirinExertsDifferentialEffectsonFunctionsofCd4+Th1,Th2,and
RegulatoryTCellClonesinHepatitisC.PLoSONE7(7):e42094.doi:10.1371/journal.pone.0042094
Editor:GoloAhlenstiel,UniversityofSydney,Australia
ReceivedFebruary17,2012;AcceptedJuly2,2012;PublishedJuly27,2012
Co
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