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