2019
T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage
Takashima S, Martin M, Jansen S, Fu Y, Bos J, Chandra D, O'Connor M, Mertelsmann A, Vinci P, Kuttiyara J, Devlin S, Middendorp S, Calafiore M, Egorova A, Kleppe M, Lo Y, Shroyer N, Cheng E, Levine R, Liu C, Kolesnick R, Lindemans C, Hanash A. T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Science Immunology 2019, 4 PMID: 31811055, PMCID: PMC7239329, DOI: 10.1126/sciimmunol.aay8556.Peer-Reviewed Original ResearchConceptsBone marrow transplantationIntestinal stem cellsDonor T cellsStem cell compartmentT cellsStem cell deathEpithelial culturesAllogeneic bone marrow transplantationDysregulated T cell activationT cell-mediated pathologyInhibition of JAK signalingStem cellsImmune-mediated damageActivated T cellsT cell activationCell compartmentCell deathTissue stem cellsPaneth cell nicheIFNg productionMarrow transplantationIntestinal immunopathologyInterferon-gHealthy miceStem cell colonies
2011
Roles of CD28, CTLA4, and Inducible Costimulator in Acute Graft-versus-Host Disease in Mice
Li J, Semple K, Suh W, Liu C, Chen F, Blazar B, Yu X. Roles of CD28, CTLA4, and Inducible Costimulator in Acute Graft-versus-Host Disease in Mice. Transplantation And Cellular Therapy 2011, 17: 962-969. PMID: 21447398, PMCID: PMC3131782, DOI: 10.1016/j.bbmt.2011.01.018.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAcute DiseaseAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteB7-1 AntigenB7-2 AntigenBone Marrow TransplantationCD28 AntigensCTLA-4 AntigenFas Ligand ProteinGraft vs Host DiseaseImmune ToleranceImmunoconjugatesInducible T-Cell Co-Stimulator ProteinInterferon-gammaLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutRadiation ChimeraT-Lymphocyte SubsetsTransplantation, HomologousTumor Necrosis Factor-alphaConceptsAllogeneic bone marrow transplantationBone marrow transplantationInducible costimulatorRole of CD28T cellsCTLA4 signalsHost diseaseMarrow transplantationMyeloablative allogeneic bone marrow transplantationPathogenic T cell responsesDevelopment of GVHDSeverity of GVHDT cell responsesT cell toleranceAbsence of B7T cell activationAcute graftAcute GVHDICOS signalingPrevents GVHDCTLA4-IgCD28 familyGVHDEffector functionsCell tolerance
2010
Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro
Cao M, Cabrera R, Xu Y, Liu C, Nelson D. Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro. International Journal Of Radiation Biology 2010, 87: 71-80. PMID: 20958220, PMCID: PMC3806980, DOI: 10.3109/09553002.2010.518208.Peer-Reviewed Original ResearchMeSH KeywordsAgedApoptosisBcl-2-Associated X ProteinCarcinoma, HepatocellularCaspase 3Cell ProliferationDose-Response Relationship, RadiationFas ReceptorFemaleGamma RaysHumansIn Vitro TechniquesInterferon-gammaInterleukin-10Liver NeoplasmsMaleMiddle AgedRadiation ToleranceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsEffector T cellsAdvanced hepatocellular carcinomaRegulatory T cellsT cellsHepatocellular carcinomaLow-dose gamma raysLow-dose irradiationApoptosis-related proteinsImmune responseLow dosesEnhanced immune responseCaspase-3Dose-dependent reductionB-cell lymphoma 2X protein expressionCell lymphoma 2Interleukin-10Peripheral bloodActive caspase-3Low-dose gamma irradiationCytokine secretionTregsLuminex assaysBlood samplesInduction of apoptosis
2009
T helper17 Cells Are Sufficient But Not Necessary to Induce Acute Graft-Versus-Host Disease
Iclozan C, Yu Y, Liu C, Liang Y, Yi T, Anasetti C, Yu X. T helper17 Cells Are Sufficient But Not Necessary to Induce Acute Graft-Versus-Host Disease. Transplantation And Cellular Therapy 2009, 16: 170-178. PMID: 19804837, PMCID: PMC3876952, DOI: 10.1016/j.bbmt.2009.09.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBody WeightBone Marrow TransplantationCD3 ComplexCells, CulturedGraft vs Host DiseaseGraft vs Host ReactionInterferon-gammaInterleukin-17MiceMice, Inbred StrainsMice, TransgenicNuclear Receptor Subfamily 1, Group F, Member 3Severity of Illness IndexSurvival AnalysisT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerTh1 CellsTime FactorsTumor Necrosis Factor-alphaWhole Body ImagingConceptsHost diseaseBALB/c recipientsBone marrow transplantation settingAcute Graft-VersusT helper17 cellsGVHD target organsInduction of graftPathogenesis of GVHDCD4 T cellsGraft-VersusGVHD developmentC recipientsT helperTh17 cellsAllogeneic recipientsAutoimmune diseasesC57BL/6 miceSyngeneic recipientsTransplantation settingGVHDT cellsIFN-gammaTarget organsSuperior expansionDiseaseCytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease
Rotolo J, Stancevic B, Lu S, Zhang J, Suh D, King C, Kappel L, Murphy G, Liu C, Fuks Z, van den Brink M, Kolesnick R. Cytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease. Blood 2009, 114: 3693-3706. PMID: 19666872, PMCID: PMC2766684, DOI: 10.1182/blood-2008-11-191148.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBone Marrow TransplantationCD8-Positive T-LymphocytesCell MembraneCeramidesCytokinesDisease Models, AnimalFemaleGraft vs Host DiseaseHepatocytesInterferon-gammaIntestine, SmallLiverLymphocyte ActivationMaleMiceMice, Inbred C57BLMice, Inbred MRL lprMice, SCIDSkinSphingomyelin PhosphodiesteraseSurvival RateT-Lymphocytes, CytotoxicConceptsHost diseaseT cellsT cell proliferation/activationAllogeneic bone marrowAcute inflammatory phaseRelevant mouse modelTumor necrosis factorCytolytic T cellsProliferation/activationCytolytic T lymphocytesPotential new targetsHost target cellsTarget cell membraneAcute graftAcute GVHDGVHD progressionCytokine stormOrgan injuryNecrosis factorGVHDInflammatory phaseRelevant graftT lymphocytesMouse modelBone marrow
2008
IL-17 contributes to CD4-mediated graft-versus-host disease
Kappel L, Goldberg G, King C, Suh D, Smith O, Ligh C, Holland A, Grubin J, Mark N, Liu C, Iwakura Y, Heller G, van den Brink M. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood 2008, 113: 945-952. PMID: 18931341, PMCID: PMC2630280, DOI: 10.1182/blood-2008-08-172155.Peer-Reviewed Original ResearchConceptsRecipients of ILT cellsGVHD mortalityHost diseaseIL-17Proinflammatory cytokinesAllogeneic bone marrow transplantAllogeneic BMT modelIL-17 contributesDonor T cellsBone marrow transplantWhole T cellsT-cell recipientsAcute graftGVHD developmentGVT activityAllograft rejectionTh17 cellsIL-17FIL-22Interleukin-17Marrow transplantAutoimmune diseasesTh1 cellsLymphoid organs
2007
IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease
Ramirez-Montagut T, Chow A, Kochman A, Smith O, Suh D, Sindhi H, Lu S, Borsotti C, Grubin J, Patel N, Terwey T, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease. The Journal Of Immunology 2007, 179: 1669-1680. PMID: 17641033, DOI: 10.4049/jimmunol.179.3.1669.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMurine renal cell carcinomaT cellsCell carcinomaGVT activityHost diseaseRenca cellsIFN-gammaTumor activityAllogeneic bone marrow transplantation modelFas ligandAbsence of graftRecipients of IFNBone marrow transplantation modelMechanism of graftMembrane-bound TNF-alphaTumor-bearing miceLethal graftLethal GVHDSevere GVHDTNF-alphaTransplantation modelTransplanted miceLytic capacitySolid tumors
2006
An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens
Wang B, He J, Liu C, Chang L. An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens. Vaccine 2006, 24: 3477-3489. PMID: 16530303, PMCID: PMC1850619, DOI: 10.1016/j.vaccine.2006.02.025.Peer-Reviewed Original ResearchConceptsTumor-associated antigensDendritic cellsModification of DCsMultiple tumor-associated antigensStrong anti-tumor responsesReactive dendritic cellsAnti-tumor responseT cell responsesLentiviral vectorsCancer-specific antigensCell antigen 2Tumor-bearing miceThymidine kinase suicide geneDC vaccinesVaccine modalitiesCancer immunotherapyCancer patientsTherapeutic injectionsTherapeutic effectExtended survivalAntigen 2Danger signalsVivo eliminationCell responsesTherapeutic potential
2005
CCR2 is required for CD8-induced graft-versus-host disease
Terwey T, Kim T, Kochman A, Hubbard V, Lu S, Zakrzewski J, Ramirez-Montagut T, Eng J, Muriglan S, Heller G, Murphy G, Liu C, Budak-Alpdogan T, Alpdogan O, van den Brink M. CCR2 is required for CD8-induced graft-versus-host disease. Blood 2005, 106: 3322-3330. PMID: 16037386, PMCID: PMC1895329, DOI: 10.1182/blood-2005-05-1860.Peer-Reviewed Original ResearchConceptsCC chemokine receptor 2Hematopoietic stem cell transplantationDevelopment of GVHDT cellsT cell migrationHost diseaseAllogeneic hematopoietic stem cell transplantationDonor-derived T cellsControl of CD8Donor-derived CD8GVHD target organsMurine bone marrow transplantation modelBone marrow transplantation modelStem cell transplantationChemokine receptor 2IFN-gamma productionWild-type CD8Alloreactive proliferationDonor CD8GVHD morbidityGVT activityTumor effectMajor complicationsCCR2 signalingCell transplantationCritical role of host γδ T cells in experimental acute graft-versus-host disease
Maeda Y, Reddy P, Lowler K, Liu C, Bishop D, Ferrara J. Critical role of host γδ T cells in experimental acute graft-versus-host disease. Blood 2005, 106: 749-755. PMID: 15797996, PMCID: PMC1895173, DOI: 10.1182/blood-2004-10-4087.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdoptive TransferAnimalsBone Marrow TransplantationCD40 LigandCell AdhesionCell CommunicationDendritic CellsFemaleGraft vs Host DiseaseInterferon-gammaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocyte SubsetsTransplantation, HomologousTumor Necrosis Factor-alphaConceptsGammadelta T cellsDendritic cellsT cellsHost diseaseAllostimulatory capacityAllogeneic bone marrow transplantation modelAllogeneic T cell proliferationDonor T cell expansionWild-type B6 recipientsHost antigen-presenting cellsTumor necrosis factor alphaExperimental acute graftWT dendritic cellsNormal dendritic cellsBone marrow transplantation modelBM transplant recipientsΓδ T cellsT cell expansionAntigen-presenting cellsNecrosis factor alphaT cell proliferationAcute graftAcute GVHDB6 recipientsGVHD mortality
2004
Blockade of CXCR3 Receptor:Ligand Interactions Reduces Leukocyte Recruitment to the Lung and the Severity of Experimental Idiopathic Pneumonia Syndrome
Hildebrandt G, Corrion L, Olkiewicz K, Lu B, Lowler K, Duffner U, Moore B, Kuziel W, Liu C, Cooke K. Blockade of CXCR3 Receptor:Ligand Interactions Reduces Leukocyte Recruitment to the Lung and the Severity of Experimental Idiopathic Pneumonia Syndrome. The Journal Of Immunology 2004, 173: 2050-2059. PMID: 15265940, DOI: 10.4049/jimmunol.173.3.2050.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsBronchoalveolar Lavage FluidCells, CulturedChemokine CXCL10Chemokine CXCL9Chemokines, CXCChemotaxis, LeukocyteCrosses, GeneticFemaleHematopoietic Stem Cell TransplantationInterferon-gammaLigandsLungLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutPneumoniaReceptors, CCR5Receptors, ChemokineReceptors, CXCR3SpleenT-Lymphocytes, CytotoxicTransplantation, HomologousTumor Necrosis Factor-alphaConceptsIdiopathic pneumonia syndromeDonor T cellsPneumonia syndromeIP-10TNF-alphaT cellsIFN-gammaCXCR3 receptorDevelopment of IPSExperimental Idiopathic Pneumonia SyndromeIP-10 protein levelsAllogeneic stem cell transplantationAllo-SCT recipientsInfiltration of IFNStandard immunosuppressive therapyT cell subsetsBronchoalveolar lavage fluidStem cell transplantationT cell recruitmentControl-treated animalsImmunosuppressive therapyLigand MigAllo-SCTFatal complicationLung injury
2003
Role of CXCR3-induced donor T-cell migration in acute GVHD
Duffner U, Lu B, Hildebrandt G, Teshima T, Williams D, Reddy P, Ordemann R, Clouthier S, Lowler K, Liu C, Gerard C, Cooke K, Ferrara J. Role of CXCR3-induced donor T-cell migration in acute GVHD. Experimental Hematology 2003, 31: 897-902. PMID: 14550805, DOI: 10.1016/s0301-472x(03)00198-x.Peer-Reviewed Original ResearchConceptsRole of CXCR3T cellsAcute GVHDDonor T cell expansionDonor T cell migrationDonor T cellsExpression of CXCR3GVHD target organsDonor cellsEffector T cellsBone marrow transplantation modelDonor T-cell functionMinor histocompatibility antigensT cell expansionWild-type B6Chemokine receptor CXCR3T cell functionWild-type T cellsWild-type donor cellsT cell migrationMigration of donorWild-type donorsAcute graftHost diseaseBMT recipientsLong‐term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti‐inflammatory effect
Nelson D, Tu Z, Soldevila‐Pico C, Abdelmalek M, Zhu H, Xu Y, Cabrera R, Liu C, Davis G. Long‐term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti‐inflammatory effect. Hepatology 2003, 38: 859-868. PMID: 14512873, DOI: 10.1002/hep.1840380412.Peer-Reviewed Original ResearchConceptsIL-10HCV RNASerum ALTCytokine productionChronic hepatitis C patientsFunctional T cell analysesSerum HCV RNA levelsHCV-specific CD4Hepatic inflammation scoresIL-10 administrationInterleukin-10 therapyPBMC cytokine productionTh2 dominant profileHCV RNA levelsHepatitis C patientsT cell analysisTh2 cytokine productionAnti-inflammatory effectsAcute flaresC patientsDisease activityMeq/mLViral burdenAdvanced fibrosisLiver biopsyRepifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect
Clouthier S, Cooke K, Teshima T, Lowler K, Liu C, Connolly K, Ferrara J. Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect. Transplantation And Cellular Therapy 2003, 9: 592-603. PMID: 14506661, DOI: 10.1016/s1083-8791(03)00230-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCD4 Lymphocyte CountCD8-Positive T-LymphocytesCell DivisionCell Line, TumorDisease Models, AnimalFemaleFibroblast Growth Factor 10Fibroblast Growth FactorsGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-2IntestinesLipopolysaccharidesLiverLymphocyte CountMiceMice, Inbred C57BLMice, Inbred StrainsRecombinant ProteinsSpleenT-LymphocytesT-Lymphocytes, CytotoxicTransplantation, HomologousTumor Necrosis Factor-alphaConceptsBone marrow transplantationAllogeneic bone marrow transplantationAllogeneic BMT recipientsSystemic GVHDGVL effectHost diseaseBMT recipientsTumor necrosis factor alphaBeneficial GVL effectInduction of GVHDSeverity of graftToxicity of GVHDMurine BMT modelBone marrow inoculumNecrosis factor alphaT cell proliferationRecombinant human keratinocyte growth factorHuman keratinocyte growth factorKeratinocyte growth factorLeukemia effectLeukemia responseSerum levelsMarrow transplantationControl miceOrgan histopathologyCD8+ T‐cell interaction with HCV replicon cells: Evidence for both cytokine‐ and cell‐mediated antiviral activity
Liu C, Zhu H, Tu Z, Xu Y, Nelson D. CD8+ T‐cell interaction with HCV replicon cells: Evidence for both cytokine‐ and cell‐mediated antiviral activity. Hepatology 2003, 37: 1335-1342. PMID: 12774012, DOI: 10.1053/jhep.2003.50207.Peer-Reviewed Original ResearchConceptsHepatitis C virusHCV replicon cellsAntiviral activityReplicon cellsHCV repliconMechanisms of HCVAnti-tumor necrosis factor alphaHCV subgenomic replicon systemAnti-interferon gammaDirect cytolytic effectHLA-A11 alleleNecrosis factor alphaHLA class IHost immune responseSubgenomic replicon systemT cell interactionsT-cell bindingHCV nonstructural proteinsCytolytic functionHCV interactionC virusSpecific lysisInfected hepatocytesTNF-alphaAntiviral effectEarly changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays
Ichiba T, Teshima T, Kuick R, Misek D, Liu C, Takada Y, Maeda Y, Reddy P, Williams D, Hanash S, Ferrara J. Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays. Blood 2003, 102: 763-771. PMID: 12663442, DOI: 10.1182/blood-2002-09-2748.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsAntigen PresentationApoptosisBone Marrow TransplantationChemotaxis, LeukocyteExpressed Sequence TagsFemaleGene Expression ProfilingGene Expression RegulationGraft vs Host DiseaseInflammationIntercellular Adhesion Molecule-1Interferon-gammaLiverLymphocyte ActivationMiceMice, Inbred C57BLOligonucleotide Array Sequence AnalysisOrgan SpecificityRadiation ChimeraSpleenT-LymphocytesTransplantation, HomologousTransplantation, IsogeneicConceptsBone marrow transplantationAllogeneic bone marrow transplantationHepatic GVHDAcute GVHDSyngeneic bone marrow transplantationMajor histocompatibility class II moleculesDonor T cellsMajor target organAcute phase proteinsClass II moleculesGene expression profilesIFN-gamma proteinNew potential molecular targetsPotential molecular targetsAcute graftHost diseaseMajor complicationsMarrow transplantationHistologic changesGVHDT cellsEndocrine functionIFN-gammaGastrointestinal tractInterferon gamma
2002
Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects
Reddy P, Teshima T, Hildebrandt G, Williams D, Liu C, Cooke K, Ferrara J. Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects. Blood 2002, 101: 2877-2885. PMID: 12433681, DOI: 10.1182/blood-2002-08-2566.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationFemaleGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-18Leukemia, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLSTAT6 Transcription FactorSurvival RateT-LymphocytesTissue DonorsTrans-ActivatorsTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationPretreatment of donorsIL-18Acute GVHDAcute graftHost diseaseLeukemia effectTransplant donorsCytotoxic T lymphocyte activityAcute GVHD mortalityIL-18 pretreatmentDonor T cellsT lymphocyte activityBM transplant recipientsIL-4 secretionSTAT6-dependent mechanismIL-18 treatmentGVHD mortalityGVL effectPreserves graftTransplant recipientsInterleukin-18Marrow transplantationBM donors
2001
Interleukin-18 Regulates Acute Graft-Versus-Host Disease by Enhancing Fas-mediated Donor T Cell Apoptosis
Reddy P, Teshima T, Kukuruga M, Ordemann R, Liu C, Lowler K, Ferrara J. Interleukin-18 Regulates Acute Graft-Versus-Host Disease by Enhancing Fas-mediated Donor T Cell Apoptosis. Journal Of Experimental Medicine 2001, 194: 1433-1440. PMID: 11714750, PMCID: PMC2193680, DOI: 10.1084/jem.194.10.1433.Peer-Reviewed Original ResearchConceptsDonor T cellsIL-18Acute GVHDHost diseaseT cellsDonor T cell expansionSerum tumor necrosis factorT helper type 1Acute Graft-VersusGamma knockout miceGVHD-related mortalityMurine bone marrow transplantation modelBone marrow transplantation modelHelper type 1T cell expansionTumor necrosis factorFas-deficient miceT cell apoptosisAcute graftGraft-VersusBMT recipientsIntestinal histopathologyTh2 responsesInterleukin-18Transplantation model
2000
Apoptosis and Regeneration of Hepatocytes during Recovery from Transient Hepadnavirus Infections
Guo J, Zhou H, Liu C, Aldrich C, Saputelli J, Whitaker T, Barrasa M, Mason W, Seeger C. Apoptosis and Regeneration of Hepatocytes during Recovery from Transient Hepadnavirus Infections. Journal Of Virology 2000, 74: 1495-1505. PMID: 10627561, PMCID: PMC111485, DOI: 10.1128/jvi.74.3.1495-1505.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDNA, ViralHepatitis BHepatitis B Virus, WoodchuckHepatitis B, ChronicInterferon-gammaLiverLiver RegenerationMarmotaMolecular Sequence DataReverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alphaViremiaConceptsRegeneration of hepatocytesHepadnavirus infectionTransient infectionHepatitis B virus infectionTumor necrosis factor alphaTransient hepadnavirus infectionsB virus infectionT cell accumulationNecrosis factor alphaCytokine expressionInfected hepatocytesFactor alphaT cellsVirus infectionInterferon gammaInfected liverHistologic analysisLiver tissueInfectionRecovery periodSignificant increaseHepatocytesInitial influxUnknown mechanismApoptosis