2020
Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells
Xie CB, Jiang B, Qin L, Tellides G, Kirkiles-Smith NC, Jane-wit D, Pober JS. Complement activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells. Journal Of Clinical Investigation 2020, 130: 3437-3452. PMID: 32191642, PMCID: PMC7324183, DOI: 10.1172/jci135060.Peer-Reviewed Original ResearchConceptsIL-15/IL-15Rα complexesIL-1βHuman endothelial cellsMembrane attack complexEndothelial cellsAcute rejectionT cellsT cell-mediated acute rejectionCell-mediated acute rejectionComplement-mediated pathologiesIL-15Rα expressionGraft endothelial cellsHuman coronary artery graftsEffector memory CD4T cell infiltrationCoronary artery graftsIL-1 receptorActive IL-1βCultured human endothelial cellsNLRP3 inflammasome assemblyNoncanonical NF-κBArtery graftAlloreactive CD8Complement membrane attack complexMemory CD4
2019
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Liu L, Fang C, Fu W, Jiang B, Li G, Qin L, Rosenbluth J, Gong G, Xie CB, Yoo P, Tellides G, Pober JS, Jane-Wit D. Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation 2019, 141: 464-478. PMID: 31744330, PMCID: PMC7035199, DOI: 10.1161/circulationaha.119.042501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDelayed Graft FunctionFemaleGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin MInflammasomesInterleukin-18Interleukin-18 Receptor alpha SubunitIsoantibodiesMiceMice, SCIDOrgan TransplantationReperfusion InjurySignal TransductionT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryDonor-specific antibodiesPeripheral helper cellsIL-18Helper cellsReperfusion injuryInterleukin-18IL-18R1Donor-specific antibody formationEndothelial cellsDelayed graft functionLate allograft lossT cell populationsAlloantibody productionAllograft lossChronic rejectionGraft functionClinical manifestationsPD-L2Antibody formationHumanized modelAllograft tissueImmunoglobulin MPatient specimensComplement activation
2016
Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice
Qin L, Li G, Kirkiles‐Smith N, Clark P, Fang C, Wang Y, Yu Z, Devore D, Tellides G, Pober J, Jane‐Wit D. Complement C5 Inhibition Reduces T Cell–Mediated Allograft Vasculopathy Caused by Both Alloantibody and Ischemia Reperfusion Injury in Humanized Mice. American Journal Of Transplantation 2016, 16: 2865-2876. PMID: 27104811, PMCID: PMC5075274, DOI: 10.1111/ajt.13834.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryAllograft vasculopathyEndothelial cell activationReperfusion injuryCell activationComplement C5 inhibitionNuclear factor kappa BSolid organ transplantsT cell infiltrationTerminal complement activationVCAM-1 expressionComplement C5 activationFactor kappa BNeutrophil infiltrationHumanized miceDiffuse stenosisIntraluminal thrombosisArterial graftsC5 inhibitionCell infiltrationHumanized modelNeointimal hyperplasiaOrgan transplantsAlloantibodiesNF-kB
2015
Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes
Jane-wit D, Surovtseva YV, Qin L, Li G, Liu R, Clark P, Manes TD, Wang C, Kashgarian M, Kirkiles-Smith NC, Tellides G, Pober JS. Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 9686-9691. PMID: 26195760, PMCID: PMC4534258, DOI: 10.1073/pnas.1503535112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBaculoviral IAP Repeat-Containing 3 ProteinClathrinComplement Membrane Attack ComplexCoronary VesselsEndocytosisEndosomesEnzyme StabilityFlow CytometryHuman Umbilical Vein Endothelial CellsHumansHydrazonesInhibitor of Apoptosis ProteinsMice, SCIDNF-kappa BProtein BiosynthesisProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRab5 GTP-Binding ProteinsRNA, Small InterferingSecretory VesiclesSignal TransductionTNF Receptor-Associated Factor 3Ubiquitin-Protein LigasesConceptsNF-κB-inducing kinaseMembrane attack complexNoncanonical NF-κBGenome-wide siRNA screenComplement membrane attack complexNIK stabilizationDynamin-dependent mannerNoncanonical NF-κB signalingEndothelial cellsActive Rab5Attack complexSiRNA screenNF-κBAkt activationCytokine-mediated activationNF-κB signalingIκB kinaseSignalosomeRab5EndosomesKinaseAktInternalizationCoronary endothelial cellsActivationEfficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9
Abrahimi P, Chang WG, Kluger MS, Qyang Y, Tellides G, Saltzman WM, Pober JS. Efficient Gene Disruption in Cultured Primary Human Endothelial Cells by CRISPR/Cas9. Circulation Research 2015, 117: 121-128. PMID: 25940550, PMCID: PMC4490936, DOI: 10.1161/circresaha.117.306290.Peer-Reviewed Original ResearchAnimalsCD4-Positive T-LymphocytesCell SeparationCells, CulturedCRISPR-Cas SystemsEndothelial Progenitor CellsFemaleFetal BloodGene DeletionGene Knockout TechniquesGenes, MHC Class IIGenetic VectorsHLA-DR AntigensHumansIntracellular Signaling Peptides and ProteinsLentivirusLymphocyte ActivationLymphocyte Culture Test, MixedMiceMice, SCIDNuclear ProteinsPrimary Cell CultureProteinsTetracyclineTrans-ActivatorsVesicular Transport Proteins
2013
Sustained delivery of proangiogenic microRNA‐132 by nanoparticle transfection improves endothelial cell transplantation
Devalliere J, Chang WG, Andrejecsk JW, Abrahimi P, Cheng CJ, Jane‐wit D, Saltzman WM, Pober JS. Sustained delivery of proangiogenic microRNA‐132 by nanoparticle transfection improves endothelial cell transplantation. The FASEB Journal 2013, 28: 908-922. PMID: 24221087, PMCID: PMC3898640, DOI: 10.1096/fj.13-238527.Peer-Reviewed Original ResearchConceptsHuman umbilical vein ECsEndothelial cellsMiR-132MicroRNA-132Cultured human umbilical vein endothelial cellsNumber of microvesselsGrowth factor-induced proliferationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsEndothelial cell transplantationCultured endothelial cellsEndogenous growth factorsEC transplantationVein endothelial cellsCell transplantationImmunodeficient miceTissue perfusionTransplantationMiR deliveryGrowth factorIntegrin αvβ3Endocytosed nanoparticlesSquare millimeterBiological effectsControl transfectionAlloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells
Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells. Circulation 2013, 128: 2504-2516. PMID: 24045046, PMCID: PMC3885874, DOI: 10.1161/circulationaha.113.002972.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyPanel reactive antibodyNuclear factor-κB signalingFactor-κB signalingAllograft vasculopathyT cellsEndothelial cellsMembrane attack complexAlloreactive T cell activationChronic antibody-mediated rejectionNoncanonical nuclear factorProinflammatory gene programAntibody-mediated rejectionDonor-specific antibodiesGraft endothelial cellsLate allograft lossAlloreactive T cellsAllogeneic endothelial cellsT cell activationAttack complexHuman T cellsAllograft lossHeart transplantationTransplantation patientsLesion pathogenesisParacrine exchanges of molecular signals between alginate-encapsulated pericytes and freely suspended endothelial cells within a 3D protein gel
Andrejecsk JW, Cui J, Chang WG, Devalliere J, Pober JS, Saltzman WM. Paracrine exchanges of molecular signals between alginate-encapsulated pericytes and freely suspended endothelial cells within a 3D protein gel. Biomaterials 2013, 34: 8899-8908. PMID: 23973174, PMCID: PMC3839675, DOI: 10.1016/j.biomaterials.2013.08.008.Peer-Reviewed Original ResearchConceptsHuman umbilical vein endothelial cellsParacrine signalsFunctioning of tissuesProper survivalEndothelial cellsUmbilical vein endothelial cellsMolecular signalsRegulated deliveryVein endothelial cellsVessel-like structuresLiving cellsProtein gelsHepatocyte growth factorTherapeutic proteinsParacrine exchangesGrowth factorMicrovascular pericytesProteinAngiogenic proteinsCellsVascular tissue engineeringHUVEC behaviorTissue constructsPericytesLocal environment
2001
HUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1
Tereb D, Kirkiles-Smith N, Kim R, Wang Y, Rudic R, Schechner J, Lorber M, Bothwell A, Pober J, Tellides G. HUMAN T CELLS INFILTRATE AND INJURE PIG CORONARY ARTERY GRAFTS WITH ACTIVATED BUT NOT QUIESCENT ENDOTHELIUM IN IMMUNODEFICIENT MOUSE HOSTS1. Transplantation 2001, 71: 1622-1630. PMID: 11435975, DOI: 10.1097/00007890-200106150-00023.Peer-Reviewed Original ResearchConceptsTumor necrosis factorHuman tumor necrosis factorArtery graftT cellsNecrosis factorPig coronary artery endothelial cellsHuman T-cell infiltrationVascular cell adhesion molecule-1Human peripheral blood mononuclearHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsHuman leukocytesEndothelial cellsMajor histocompatibility complex antigensCell adhesion molecule-1Graft endothelial cellsT-cell infiltratesBeige mouse modelCoronary artery endothelial cellsT cell infiltrationCoronary artery graftsBlood mononuclear cellsPeripheral blood mononuclearCoronary artery segmentsAdhesion molecule-1Endothelial cell activation by tumor necrosis factor elicits human antiporcine cell-mediated rejection responses
Kirkiles-Smith NC, Tereb DA, Kim RW, McNiff JM, Schechner JS, Lorber MI, Pober JS, Tellides G. Endothelial cell activation by tumor necrosis factor elicits human antiporcine cell-mediated rejection responses. Transplantation Proceedings 2001, 33: 412-413. PMID: 11266888, DOI: 10.1016/s0041-1345(00)02072-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCytokinesEndothelium, VascularGraft RejectionHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansLymphocyte ActivationMiceMice, SCIDModels, AnimalSkin TransplantationSpecies SpecificitySwineT-LymphocytesTransplantation ChimeraTransplantation ToleranceTransplantation, HeterologousTumor Necrosis Factor-alpha
2000
In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse
Schechner J, Nath A, Zheng L, Kluger M, Hughes C, Sierra-Honigmann M, Lorber M, Tellides G, Kashgarian M, Bothwell A, Pober J. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 9191-9196. PMID: 10890921, PMCID: PMC16844, DOI: 10.1073/pnas.150242297.Peer-Reviewed Original ResearchHuman TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts
Kirkiles-Smith N, Tereb D, Kim R, McNiff J, Schechner J, Lorber M, Pober J, Tellides G. Human TNF Can Induce Nonspecific Inflammatory and Human Immune-Mediated Microvascular Injury of Pig Skin Xenografts in Immunodeficient Mouse Hosts. The Journal Of Immunology 2000, 164: 6601-6609. PMID: 10843720, DOI: 10.4049/jimmunol.164.12.6601.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAdultAnimalsCell Adhesion MoleculesDose-Response Relationship, ImmunologicDrug SynergismEndothelium, VascularGraft RejectionHistocompatibility AntigensHumansInterferon-gammaMiceMice, Inbred C57BLMice, SCIDMicrocirculationSevere Combined ImmunodeficiencySkin TransplantationSwineT-LymphocytesTransplantation, HeterologousTumor Necrosis Factor-alphaUp-RegulationConceptsHuman T-cell infiltrationPig skin xenograftsT cell infiltrationSkin xenograftsCell infiltrationHuman TNFIFN-gammaE-selectinT cell-mediated rejectionEndothelial cellsAdhesion moleculesCytokine-mediated injuryNonspecific inflammatory damagePig skin graftsCell-mediated rejectionAppropriate therapeutic targetsImmunodeficient mouse modelPorcine E-selectinEndothelial adhesion moleculesPorcine IFN-gammaClass II moleculesHuman skin allograftsMHC class IPorcine endothelial cellsImmunodeficient mouse hostsInterferon-γ elicits arteriosclerosis in the absence of leukocytes
Tellides G, Tereb D, Kirkiles-Smith N, Kim R, Wilson J, Schechner J, Lorber M, Pober J. Interferon-γ elicits arteriosclerosis in the absence of leukocytes. Nature 2000, 403: 207-211. PMID: 10646607, DOI: 10.1038/35003221.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsArteriosclerosisCell DivisionCells, CulturedCoronary VesselsHistocompatibility AntigensHumansImage Processing, Computer-AssistedImmunohistochemistryInterferon-gammaLeukocytesMiceMice, SCIDMuscle, Smooth, VascularPlatelet-Derived Growth FactorReceptor, Platelet-Derived Growth Factor betaSwineTransplantation, HeterologousConceptsVascular smooth muscle cellsGraft arteriosclerosisIntimal expansionAbsence of leukocytesLesions of atherosclerosisSmooth muscle cellsAllogeneic transplantationArteriosclerotic changesAtheroma formationCytokine interferonExogenous IFNAntigen presentationT cellsImmunodeficient miceMononuclear leukocytesMouse modelArterial intimaIFNMuscle cellsArteriosclerosisLeukocytesHuman arteriesAtherosclerosisCellsTransplantation
1999
HUMAN ALLOGENEIC VASCULAR REJECTION AFTER ARTERIAL TRANSPLANTATION AND PERIPHERAL LYMPHOID RECONSTITUTION IN SEVERE COMBINED IMMUNODEFICIENT MICE1
Lorber MI, Wilson JH, Robert ME, Schechner JS, Kirkiles N, Qian HY, Askenase PW, Tellides G, Pober JS. HUMAN ALLOGENEIC VASCULAR REJECTION AFTER ARTERIAL TRANSPLANTATION AND PERIPHERAL LYMPHOID RECONSTITUTION IN SEVERE COMBINED IMMUNODEFICIENT MICE1. Transplantation 1999, 67: 897-903. PMID: 10199740, DOI: 10.1097/00007890-199903270-00018.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsHuman CD3Vascular rejectionTransplantation modelAllogeneic human peripheral blood mononuclear cellsAllogeneic peripheral blood mononuclear cellsHuman dermal microvesselsBlood mononuclear cellsHuman arteriesSmooth muscle alpha-actinSmooth muscle cellsMuscle alpha-actinArterial transplantationPerforin stainingAllograft rejectionAlloimmune injuryDR antibodiesLymphocyte engraftmentMedial necrosisHLA-DRLymphocytic infiltrationLymphoid infiltrationControl miceInfrarenal aorta
1998
Allogeneic and xenogeneic vascular injury and protection
Pober JS, Schechner JS, Murray AG, Sultan P, Kirkiles N, Tereb D, Wilson J, McNiff JM, Askenase PW, Tellides G, Lorber MI. Allogeneic and xenogeneic vascular injury and protection. Transplantation Proceedings 1998, 30: 4168-4169. PMID: 9865336, DOI: 10.1016/s0041-1345(98)01381-5.Peer-Reviewed Original ResearchDermal Microvascular Injury in the Human Peripheral Blood Lymphocyte Reconstituted-Severe Combined Immunodeficient (HuPBL-SCID) Mouse/Skin Allograft Model Is T Cell Mediated and Inhibited by a Combination of Cyclosporine and Rapamycin
Murray A, Schechner J, Epperson D, Sultan P, McNiff J, Hughes C, Lorber M, Askenase P, Pober J. Dermal Microvascular Injury in the Human Peripheral Blood Lymphocyte Reconstituted-Severe Combined Immunodeficient (HuPBL-SCID) Mouse/Skin Allograft Model Is T Cell Mediated and Inhibited by a Combination of Cyclosporine and Rapamycin. American Journal Of Pathology 1998, 153: 627-638. PMID: 9708821, PMCID: PMC1852982, DOI: 10.1016/s0002-9440(10)65604-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCD8-Positive T-LymphocytesCyclosporineDrug Therapy, CombinationEndothelium, VascularEnzyme-Linked Immunosorbent AssayFlow CytometryGenes, MHC Class IIGraft RejectionHumansImmunosuppressive AgentsKeratinocytesMiceMice, SCIDMicrocirculationPolyenesSirolimusSkinSkin TransplantationT-LymphocytesTransplantation, HomologousVascular Cell Adhesion Molecule-1ConceptsPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsSkin allograft modelMicrovascular injuryT cellsCell infiltrateAllograft modelWhole peripheral blood mononuclear cellsT cell-dependent mechanismT cell-mediated rejectionHuman natural killer cellsSCID/beige miceEndothelial cell sloughingT Cell-MediatedCell-mediated rejectionCombination of cyclosporineT-cell infiltratesCell-dependent mechanismMononuclear cell infiltrateNatural killer cellsMononuclear cell infiltrationBlood mononuclear cellsSkin graft modelHuman immune responseImmunoglobulin G antibodies
1997
Pig but not human interferon-γ initiates human cell-mediated rejection of pig tissue in vivo
Sultan P, Murray A, McNiff J, Lorber M, Askenase P, Bothwell A, Pober J. Pig but not human interferon-γ initiates human cell-mediated rejection of pig tissue in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 8767-8772. PMID: 9238052, PMCID: PMC23121, DOI: 10.1073/pnas.94.16.8767.Peer-Reviewed Original ResearchConceptsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsPig skin graftsCell-mediated rejectionBlood mononuclear cellsIFN-gammaMononuclear cellsSkin graftsDermal microvesselsMajor histocompatibility complex (MHC) molecule expressionT cell-mediated rejectionPerivascular mononuclear cell infiltratesClass II major histocompatibility complex moleculesMononuclear cell infiltrateMajor histocompatibility complex moleculesTumor necrosis factorEvidence of injuryHistocompatibility complex moleculesPig endothelial cellsCell infiltrateIntradermal injectionMolecule expressionSparse infiltrateIntraperitoneal inoculationMouse microvesselsBlockade of CD2-LFA-3 interactions protects human skin allografts in immunodeficient mouse/human chimeras
Sultan P, Schechner J, McNiff J, Hochman P, Hughes C, Lorber M, Askenase P, Pober J. Blockade of CD2-LFA-3 interactions protects human skin allografts in immunodeficient mouse/human chimeras. Nature Biotechnology 1997, 15: 759-762. PMID: 9255790, DOI: 10.1038/nbt0897-759.Peer-Reviewed Original ResearchConceptsSkin graftsLFA-3Human T-cell infiltrationIsotype-matched control antibodyT cell infiltrationSkin graft rejectionHuman skin graftsHuman skin allograftsCD2-LFA-3 interactionHuman LFA-3Microvascular injuryGraft rejectionLeukocyte infiltrationSkin allograftsImmune modulatorsControl antibodyInjury modelImmunodeficient miceImmune reactionsMouse/human chimeraMurine mAbsCD2 interactionPrincipal ligandGraftInjury
1994
Human T-cell-mediated destruction of allogeneic dermal microvessels in a severe combined immunodeficient mouse.
Murray AG, Petzelbauer P, Hughes CC, Costa J, Askenase P, Pober JS. Human T-cell-mediated destruction of allogeneic dermal microvessels in a severe combined immunodeficient mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 9146-9150. PMID: 8090783, PMCID: PMC44764, DOI: 10.1073/pnas.91.19.9146.Peer-Reviewed Original ResearchConceptsSignificant T-cell infiltrationT-cell-mediated injuryT cell-mediated destructionVascular cell adhesion molecule-1Human microvesselsSevere combined immunodeficient (SCID) miceMajor histocompatibility complex (MHC) class II moleculesCell adhesion molecule-1Human allograft rejectionT-cell infiltratesT cell infiltrationCombined Immunodeficient MiceImmunodeficient mouse modelAdhesion molecule-1Human skin graftsClass II moleculesPotential therapeutic reagentSmall animal modelsHuman vascular endotheliumAllograft rejectionSkin rejectionMouse microvesselsSkin graftsT cellsImmunodeficient mice