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 pathogenesisRapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells
Wang C, Yi T, Qin L, Maldonado RA, von Andrian UH, Kulkarni S, Tellides G, Pober JS. Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells. Journal Of Clinical Investigation 2013, 123: 1677-1693. PMID: 23478407, PMCID: PMC3613923, DOI: 10.1172/jci66204.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsArteriesB7-H1 AntigenCD4-Positive T-LymphocytesCell ProliferationCells, CulturedCoculture TechniquesFemaleGene ExpressionGene Knockdown TechniquesHuman Umbilical Vein Endothelial CellsHumansImmunosuppression TherapyInterleukin-6Lymphocyte ActivationMiceMice, SCIDProgrammed Cell Death 1 Ligand 2 ProteinRegulatory-Associated Protein of mTORRNA, Small InterferingSirolimusT-Lymphocytes, RegulatoryTOR Serine-Threonine KinasesTranscriptional ActivationTransplantation, HomologousConceptsEffect of rapamycinT cellsEndothelial cellsAllograft rejectionHuman endothelial cellsPD-L1PD-L2Allogeneic regulatory T cellsHuman-mouse chimeric modelInhibitory molecule PD-L1Inflammatory cytokines IL-6Alloantigen-specific mannerAllograft endothelial cellsHuman arterial allograftsImmune-mediated rejectionGraft endothelial cellsEffector T cellsRegulatory T cellsMemory T cellsT cell responsesAntigen-presenting cellsCytokines IL-6Mock-treated cellsAllogeneic CD4Effector cytokines
2011
Neutralizing IL-6 Reduces Human Arterial Allograft Rejection by Allowing Emergence of CD161+ CD4+ Regulatory T Cells
Fogal B, Yi T, Wang C, Rao DA, Lebastchi A, Kulkarni S, Tellides G, Pober JS. Neutralizing IL-6 Reduces Human Arterial Allograft Rejection by Allowing Emergence of CD161+ CD4+ Regulatory T Cells. The Journal Of Immunology 2011, 187: 6268-6280. PMID: 22084439, PMCID: PMC3237826, DOI: 10.4049/jimmunol.1003774.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCell DifferentiationCells, CulturedChemotaxis, LeukocyteCoculture TechniquesCoronary VesselsDisease Models, AnimalEndothelium, VascularFemaleGraft RejectionHuman Umbilical Vein Endothelial CellsHumansInterleukin-6MiceMice, SCIDMyocytes, Smooth MuscleNeutralization TestsNK Cell Lectin-Like Receptor Subfamily BT-Lymphocytes, RegulatoryConceptsRegulatory T cellsT cell infiltrationMemory T cellsT cell proliferationT cellsIL-6Allograft rejectionCell infiltrationIntimal expansionEffector memory T cellsHuman coronary artery segmentsEndothelial cellsEnhanced T cell proliferationHuman allograft rejectionT-cell infiltratesExpression of Foxp3Coronary artery segmentsCell proliferationMHC class IIIL-6 transcriptsT cell activationImmunodeficient mouse hostsHuman IL-6Allograft vesselsPerioperative injuryReperfusion Injury Intensifies the Adaptive Human T Cell Alloresponse in a Human-Mouse Chimeric Artery Model
Yi T, Fogal B, Hao Z, Tobiasova Z, Wang C, Rao DA, Al-Lamki RS, Kirkiles-Smith NC, Kulkarni S, Bradley JR, Bothwell AL, Sessa WC, Tellides G, Pober JS. Reperfusion Injury Intensifies the Adaptive Human T Cell Alloresponse in a Human-Mouse Chimeric Artery Model. Arteriosclerosis Thrombosis And Vascular Biology 2011, 32: 353-360. PMID: 22053072, PMCID: PMC3262100, DOI: 10.1161/atvbaha.111.239285.Peer-Reviewed Original ResearchConceptsArtery segmentsReperfusion injuryNonimmune injuryHuman artery segmentsHuman-mouse chimeric modelInfrarenal aortic interposition graftsT-cell-mediated injuryMouse hostHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsCell-mediated injuryT cell alloresponseBlood mononuclear cellsAdaptive immune responsesAortic interposition graftsImmunodeficient mouse hostsGraft survivalInterposition graftImmunologic rejectionMononuclear cellsT cellsImmune responseMinimal sequelaeChimeric modelInjuryPeroxisome Proliferator–Activated Receptor-γ Agonists Prevent In Vivo Remodeling of Human Artery Induced by Alloreactive T Cells
Tobiasova Z, Zhang L, Yi T, Qin L, Manes TD, Kulkarni S, Lorber MI, Rodriguez FC, Choi JM, Tellides G, Pober JS, Kawikova I, Bothwell AL. Peroxisome Proliferator–Activated Receptor-γ Agonists Prevent In Vivo Remodeling of Human Artery Induced by Alloreactive T Cells. Circulation 2011, 124: 196-205. PMID: 21690493, PMCID: PMC3347886, DOI: 10.1161/circulationaha.110.015396.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnilidesAnimalsArteriesCell MovementCell ProliferationCytokinesGraft RejectionHumansHypoglycemic AgentsImmunologic MemoryIsoantigensMiceMice, SCIDPioglitazonePPAR gammaProstaglandin D2SuperantigensThiazolidinedionesT-LymphocytesTransplantation, HeterologousTransplantation, HomologousConceptsT cell responsesMemory T cellsVascular graft rejectionT cellsPPARγ agonistsVascular rejectionGraft rejectionAllogeneic human peripheral blood mononuclear cellsHuman memory T-cell responsesHuman T cell responsesMemory T cell responsesHuman peripheral blood mononuclear cellsTranscription factor peroxisome proliferator-activated receptorPeripheral blood mononuclear cellsChronic graft lossPeroxisome proliferator-activated receptorT-cell infiltratesAllogeneic T cellsAlloreactive T cellsBlood mononuclear cellsAlloantigen-induced proliferationVascular cell activationHuman arteriesProliferator-activated receptorEffects of PPARγ