2019
Progenitor-derived human endothelial cells evade alloimmunity by CRISPR/Cas9-mediated complete ablation of MHC expression
Merola J, Reschke M, Pierce RW, Qin L, Spindler S, Baltazar T, Manes TD, Lopez-Giraldez F, Li G, Bracaglia LG, Xie C, Kirkiles-Smith N, Saltzman WM, Tietjen GT, Tellides G, Pober JS. Progenitor-derived human endothelial cells evade alloimmunity by CRISPR/Cas9-mediated complete ablation of MHC expression. JCI Insight 2019, 4 PMID: 31527312, PMCID: PMC6824302, DOI: 10.1172/jci.insight.129739.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsbeta 2-MicroglobulinCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedCRISPR-Cas SystemsDisease Models, AnimalEndothelial CellsEndothelial Progenitor CellsFemaleFetal BloodGene Knockout TechniquesGraft RejectionHealthy VolunteersHumansIsoantibodiesKiller Cells, NaturalLymphocyte ActivationMiceMicrovesselsNuclear ProteinsOrgan TransplantationPrimary Cell CultureTissue EngineeringTrans-ActivatorsConceptsDonor-specific antibodiesClass II transactivatorEndothelial cellsMHC expressionAllogeneic natural killer (NK) cellsT effector memory cellsEffector memory T cellsClass IClass II major histocompatibility complex moleculesEffector memory cellsMHC molecule expressionMemory T cellsNatural killer cellsAlloreactive cytotoxic T lymphocytesAllogeneic endothelial cellsMajor histocompatibility complex moleculesCytotoxic T lymphocytesClass I MHC moleculesHistocompatibility complex moleculesI MHC moleculesAllogeneic CD4Donor leukocytesHuman endothelial cellsGraft perfusionKiller cells
2013
Alloantibody 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 pathogenesis
2011
Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells
Lebastchi AH, Khan SF, Qin L, Li W, Zhou J, Hibino N, Yi T, Rao DA, Pober JS, Tellides G. Transforming Growth Factor Beta Expression by Human Vascular Cells Inhibits Interferon Gamma Production and Arterial Media Injury by Alloreactive Memory T Cells. American Journal Of Transplantation 2011, 11: 2332-2341. PMID: 21812925, PMCID: PMC3203343, DOI: 10.1111/j.1600-6143.2011.03676.x.Peer-Reviewed Original ResearchConceptsEffector T cellsMemory T cellsNaïve T cellsT cellsIL-17Vascular cellsEffector memory T cellsAlloreactive memory T cellsGrowth factor-beta expressionMedial smooth muscle cellsHuman effector memory T cellsHuman coronary artery graftsIL-17 productionCoronary artery graftsIFN-γ productionAllogeneic endothelial cellsInterferon-gamma productionDevelopment of arteriosclerosisExpression of TGFRole of TGFSmooth muscle cellsImmunodeficient mouse hostsHuman T cellsIntimal compartmentMedial infiltration
2009
Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death
Choy JC, Pober JS. Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death. American Journal Of Transplantation 2009, 9: 2281-2291. PMID: 19663890, PMCID: PMC3505447, DOI: 10.1111/j.1600-6143.2009.02771.x.Peer-Reviewed Original ResearchConceptsHuman CD8 T cellsCD8 T cellsInducible NO synthaseT cellsActivated T cellsNitric oxideDeprivation-induced cell deathCell deathAllogeneic endothelial cellsT cell proliferationActivation-induced cell deathCytokine deprivationGeneration of NOT cell deathExogenous nitric oxideHuman T cellsNO augmentsAllogeneic responseS-nitrosylationNO synthaseProtective effectActivity of caspasesEndothelial cellsPharmacological inhibitorsDeathParacrine Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death (141.3)
Choy J, Pober J. Paracrine Generation of NO by Bystander Human CD8 T Cells Augments Allogeneic Responses by Inhibiting Cytokine Deprivation-Induced Cell Death (141.3). The Journal Of Immunology 2009, 182: 141.3-141.3. DOI: 10.4049/jimmunol.182.supp.141.3.Peer-Reviewed Original ResearchHuman CD8 T cellsCD8 T cellsT cellsActivated T cellsDeprivation-induced cell deathCell deathAllogeneic endothelial cellsT cell proliferationActivation-induced cell deathCytokine deprivationHuman T cellsProtein expression levelsNO augmentsAllogeneic responseS-nitrosylationProtective effectExogenous NOActivity of caspasesEndothelial cellsPharmacological inhibitorsDeathBcl-2Cell proliferationExpression levelsINOS
2008
Amelioration of Human Allograft Arterial Injury by Atorvastatin or Simvastatin Correlates With Reduction of Interferon-γ Production by Infiltrating T Cells
Yi T, Rao DA, Tang PC, Wang Y, Cuchara LA, Bothwell AL, Colangelo CM, Tellides G, Pober JS, Lorber MI. Amelioration of Human Allograft Arterial Injury by Atorvastatin or Simvastatin Correlates With Reduction of Interferon-γ Production by Infiltrating T Cells. Transplantation 2008, 86: 719-727. PMID: 18791454, PMCID: PMC2650813, DOI: 10.1097/tp.0b013e318183eefa.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsGraft arteriosclerosisIFN-gamma productionIFN-gammaT cellsAllogeneic human peripheral blood mononuclear cellsHuman leukocyte antigen-DR expressionHuman IFN-gammaEndothelial cellsCoenzyme A (HMG-CoA) reductase inhibitorsT cell alloresponsesT cell accumulationAllogeneic endothelial cellsLong-term outcomesBlood mononuclear cellsEffect of statinsInterferon-γ ProductionA Reductase InhibitorsAortic interposition graftsReplication-deficient adenovirusVascular endothelial cellsTransplant arteryHuman artery segmentsStatin administration
1999
Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL.
Biedermann B, Pober J. Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL. The Journal Of Immunology 1999, 162: 7022-30. PMID: 10358144, DOI: 10.4049/jimmunol.162.12.7022.Peer-Reviewed Original ResearchConceptsTarget cell contactB lymphoblastoid cellsLittle IFN-gammaIFN-gammaEndothelial cellsCTL clonesClass I MHC-restricted CTLAbsence of ECExpression of CD40LAllogeneic endothelial cellsIFN-gamma secretionIL-4 secretionCell contactHuman vascular endothelial cellsVascular endothelial cellsCTL subsetsCD40L expressionCTL linesCD40 ligandT cellsAlloreactive CTLArterial intimaClonal expansionCTLCultured HUVECs
1998
Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion.
Collinge M, Pardi R, Bender J. Class II transactivator-independent endothelial cell MHC class II gene activation induced by lymphocyte adhesion. The Journal Of Immunology 1998, 161: 1589-93. PMID: 9712019, DOI: 10.4049/jimmunol.161.4.1589.Peer-Reviewed Original ResearchConceptsClass II transactivatorNK cellsIFN-gamma-dependent mechanismIFN-gamma-independent mannerLymphocyte adhesionMHC class II expressionHLA-DR alpha mRNAHLA-DR expressionMHC class II moleculesNK cell activationAllogeneic endothelial cellsClass II expressionIFN-gamma-induced MHC class II expressionClass II moleculesAlpha mRNA expressionCell linesHLA-DRIFN-gammaCell activationMRNA expressionEndothelial cellsAlpha mRNACellsPromoter constructsActivation
1995
Human vascular smooth muscle cells poorly co-stimulate and actively inhibit allogeneic CD4+ T cell proliferation in vitro.
Murray AG, Libby P, Pober JS. Human vascular smooth muscle cells poorly co-stimulate and actively inhibit allogeneic CD4+ T cell proliferation in vitro. The Journal Of Immunology 1995, 154: 151-61. PMID: 7995934, DOI: 10.4049/jimmunol.154.1.151.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsT cell proliferationClass II moleculesHuman vascular smooth muscle cellsMHC class II moleculesT cellsIL-2 productionSmooth muscle cellsEndothelial cellsCell proliferationFunctional MHC class II moleculesII-positive endothelial cellsIL-2-producing cellsMuscle cellsPre-activated T cellsAllogeneic endothelial cellsNitric oxide synthesisInhibition of proliferationVSMC-conditioned mediumAllogeneic CD4CD25 expressionInhibits CD4Immunologic functionVSMC expressionSaphenous vein
1994
Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells.
Epperson DE, Pober JS. Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells. The Journal Of Immunology 1994, 153: 5402-12. PMID: 7989746, DOI: 10.4049/jimmunol.153.12.5402.Peer-Reviewed Original ResearchConceptsCD8 T cellsMemory CD8 T cellsT cell proliferative responsesAllogeneic endothelial cellsCell proliferative responsesT cellsAdhesion molecule-1Endothelial cellsCD8/IL-2Proliferative responseMolecule-1CD4 T cell proliferative responsesLate activation Ag-4Human CD8 T cellsVascular cell adhesion molecule-1Class II MHC expressionIntercellular adhesion molecule-1Cell adhesion molecule-1CD4 T cellsIFN-gamma secretionOrgan graft rejectionIL-2R alpha subunitIntercellular adhesion molecule-2CD8 cells
1991
Signal requirements for the generation of CD4+ and CD8+ T-cell responses to human allogeneic microvascular endothelium.
Pardi R, Bender J. Signal requirements for the generation of CD4+ and CD8+ T-cell responses to human allogeneic microvascular endothelium. Circulation Research 1991, 69: 1269-1279. PMID: 1934357, DOI: 10.1161/01.res.69.5.1269.Peer-Reviewed Original ResearchConceptsT cell precursorsEndothelial cellsInterleukin-2T cellsT lymphocytesMicrovascular endotheliumT cell-mediated immune responsesMajor T cell subsetsSpecific cytotoxic T lymphocytesMonocyte/macrophage seriesMHC class II determinantsCD3/T cell receptor complexIndividual cell subsetsGeneration of CD4Effector T cellsClass II determinantsT cell responsesT cell subsetsAdoptive transfer experimentsAllogeneic endothelial cellsClass I determinantsSelf-MHC moleculesCytotoxic T lymphocytesMonocytes/macrophagesT cell receptor complex
1990
T-cell receptor-negative natural killer cells display antigen-specific cytotoxicity for microvascular endothelial cells.
Bender J, Pardi R, Engleman E. T-cell receptor-negative natural killer cells display antigen-specific cytotoxicity for microvascular endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 6949-6953. PMID: 2402485, PMCID: PMC54659, DOI: 10.1073/pnas.87.18.6949.Peer-Reviewed Original ResearchConceptsMicrovascular endothelial cellsEndothelial cellsNK cellsNatural killer cell targetsNatural killer cellsAllogeneic endothelial cellsAntigen-specific cytotoxicityNK cell linesCD3/T cell receptorLevel of adherenceEC linesHuman microvascular endothelial cellsT cell receptorOrgan allograftsGamma chain geneKiller cellsLymphoid cellsSpecific cytotoxicityCell targetsNegative cellsCell linesHuman erythroleukemia cellsSelective cytotoxicityTi moleculesCytotoxicity
1989
EVIDENCE THAT CYTOTOXIC LYMPHOCYTES ALTER AND TRAVERSE ALLOGENEIC ENDOTHELIAL CELL MONOLAYERS
BENDER J, PARDI R, KOSEK J, ENGLEMAN E. EVIDENCE THAT CYTOTOXIC LYMPHOCYTES ALTER AND TRAVERSE ALLOGENEIC ENDOTHELIAL CELL MONOLAYERS. Transplantation 1989, 47: 1047-1052. PMID: 2660343, DOI: 10.1097/00007890-198906000-00026.Peer-Reviewed Original ResearchConceptsAllogeneic endothelial cellsEndothelial cellsClass II major histocompatibility complex antigensMajor histocompatibility complex antigensLymphocyte-EC adhesionHistocompatibility complex antigensEC monolayersSame morphologic changesAllogeneic lymphocytesLymphocyte subsetsLymphocyte subpopulationsAutologous combinationsEndothelial cell monolayersSuch lymphocytesSurface phenotypeComplex antigensIntact EC monolayerRecombinant cytokinesMorphologic changesLymphocytesCell monolayersEC barrierFunctional consequencesCurrent findingsCellular interactions
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