Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss in Human Peripheral Blood T Lymphocytes 英文参考文献.docVIP

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Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss in Human Peripheral Blood T Lymphocytes 英文参考文献.doc

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Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss in Human Peripheral Blood T Lymphocytes 英文参考文献

ExtendedInterferon-AlphaTherapyAccelerates TelomereLengthLossinHumanPeripheralBloodT Lymphocytes JoelM.O’Bryan1,JamesA.Potts1,HerbertL.Bonkovsky2,3,AnujaMathew1*,AlanL.Rothman1,4,forthe HALT-CTrialGroup 1Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2Department of Medicine, University of ConnecticutHealthCenter,Farmington,Connecticut,UnitedStatesofAmerica,3CarolinasMedicalCenter,Charlotte,NorthCarolina,UnitedStatesofAmerica,4Institute forImmunologyandInformatics,UniversityofRhodeIsland,Providence,RhodeIsland,UnitedStatesofAmerica Abstract Background:TypeIinterferonshavepleiotropiceffectsonhostcells,includinginhibitingtelomeraseinlymphocytesand antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in averagetelomerelengthinperipheralbloodTlymphocytes. Methods/PrincipalFindings:Usingaflowcytometry-basedtelomerelengthassayonperipheralbloodmononuclearcell samplesfromtheHepatitis-CAntiviralLong-termTreatmentagainstCirrhosis(HALT-C)study,wemeasuredTcelltelomere lengthsatscreeningandatmonths21and45in29Hepatitis-Cvirusinfectedsubjects.Thesesubjectshadfailedtoachieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNa group for an additional3.5years.Significanttelomerelossinna?¨veTcellsoccurredinthefirst21monthsintheinterferon-alphagroup. Telomerelossesweresimilarinbothgroupsduringthefinaltwoyears.ExpansionofCD8 CD45RA+CD57 memoryTcells + + + and an inverse correlation of alanine aminotransferase levels with na?¨ve CD8 T cell telomere loss were observed in the controlgroupbutnotintheinterferon-alphagroup.TelomerelengthatscreeninginverselycorrelatedwithHepatitis-Cviral loadandbodymassindex. Conclusions/Significance:Sustainedinterferon-alphatreatmentincreasedtelomerelossi