2018
Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection
Lim S, Kirkiles-Smith NC, Pober JS, Bothwell ALM, Choi JM. Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection. Biomaterials 2018, 183: 128-138. PMID: 30165256, PMCID: PMC6141312, DOI: 10.1016/j.biomaterials.2018.08.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCell-Penetrating PeptidesCTLA-4 AntigenCytokinesEndothelial CellsFemaleGraft RejectionHuman Umbilical Vein Endothelial CellsHumansLymphocyte ActivationMice, Inbred BALB CMice, KnockoutMice, SCIDMicrovesselsReceptors, ChemokineSkinSkin TransplantationT-LymphocytesConceptsT cell responsesHuman T cell responsesT cell infiltrationHuman T cellsT cellsCell responsesGraft rejectionCell infiltrationSCID/beige miceCell-permeable peptideBlood cytokine levelsT cell alloresponsesCD8 T cellsChemokine receptor expressionGranzyme B expressionAlloreactive T cellsSignificant side effectsDouble knockout miceHuman T cell activationBcl-2-transduced human umbilical vein endothelial cellsT cell activationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsSystemic immunosuppressantsAllograft rejection
2015
dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis
Lim S, Kim WJ, Kim YH, Lee S, Koo JH, Lee JA, Yoon H, Kim DH, Park HJ, Kim HM, Lee HG, Yun Kim J, Lee JU, Hun Shin J, Kyun Kim L, Doh J, Kim H, Lee SK, Bothwell AL, Suh M, Choi JM. dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. Nature Communications 2015, 6: 8244. PMID: 26372309, PMCID: PMC4579786, DOI: 10.1038/ncomms9244.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisT cellsAutoimmune encephalomyelitisCytotoxic T-lymphocyte antigen-4T-lymphocyte antigen-4T helper 17 (Th17) cellsCNS inflammatory diseasesTherapeutic mouse modelsEffector T cellsHelper 17 cellsT helper 1Blood-brain barrierCentral nervous systemHuman T cellsHelper 1Antigen-4Inflammatory diseasesMouse modelNervous systemCurrent drugsResident cellsBrain tissueEffective agentCell-permeable peptide
2012
The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases
Choi JM, Bothwell AL. The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases. Molecules And Cells 2012, 33: 217-222. PMID: 22382683, PMCID: PMC3887706, DOI: 10.1007/s10059-012-2297-y.Peer-Reviewed Original ResearchConceptsPeroxisome proliferator-activated receptorIndependent regulatory mechanismsImportant regulatory roleNuclear receptor proteinsT helper cell differentiationTranscription factorsCellular differentiationNuclear receptor peroxisome proliferator-activated receptorGene expressionRegulatory mechanismsDiverse rolesHelper cell differentiationT cell survivalPPARβ/δCell differentiationRegulatory roleImportant regulatorReceptor proteinNuclear receptorsT cell activationProliferator-activated receptorAutoimmune diseasesLigand treatmentProteinSynthetic ligands
2011
Reperfusion 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
2008
Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis
Choi JM, Kim SH, Shin JH, Gibson T, Yoon BS, Lee DH, Lee SK, Bothwell AL, Lim JS, Lee SK. Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 19875-19880. PMID: 19066215, PMCID: PMC2604944, DOI: 10.1073/pnas.0805198105.Peer-Reviewed Original ResearchConceptsCollagen-induced arthritisT cell activationCTLA-4Human umbilical vein endothelial cellsCell activationInflammatory cytokine productionErosion of cartilageCytoplasmic domainEffective therapeutic approachActivated T cellsUmbilical vein endothelial cellsCell-permeable formT cell receptor-proximal signalingVein endothelial cellsAntibody levelsRheumatoid arthritisAutoimmune diseasesCytokine productionHuman CTLT cellsTherapeutic approachesCell-permeable recombinant proteinArthritisTransdermal administrationMouse T cell activationAmelioration 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
2007
Regulatory Transplantation Tolerance and “Stemness”: Evidence That Foxp3 May Play a Regulatory Role in SOCS-3 Gene Transcription
Muthukumarana P, Chae WJ, Maher S, Rosengard BR, Bothwell AL, Metcalfe SM. Regulatory Transplantation Tolerance and “Stemness”: Evidence That Foxp3 May Play a Regulatory Role in SOCS-3 Gene Transcription. Transplantation 2007, 84: s6-s11. PMID: 17632414, DOI: 10.1097/01.tp.0000269116.06510.db.Peer-Reviewed Original ResearchConceptsExpression of Foxp3Wt-Foxp3Regulatory transplantation toleranceSOCS-3Immune effector cellsStem cell-related factorsHuman T cell lineCell-related factorsT cell linesJurkat human T cell lineSOCS-3 transcriptsLIF transcriptionSuppressor of cytokineTransplantation toleranceEffector cellsT lymphocytesFoxp3Inhibitory factorKey mediatorT cell signal transductionAxotrophinTregsFurther evidenceTranscriptional activityRegulatory role
2006
Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammation
Das J, Eynott P, Jupp R, Bothwell A, Van Kaer L, Shi Y, Das G. Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammation. Nature Medicine 2006, 12: 1345-1346. PMID: 17151684, DOI: 10.1038/nm1206-1345.Peer-Reviewed Original ResearchDecreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study
Kawikova I, Leckman JF, Kronig H, Katsovich L, Bessen DE, Ghebremichael M, Bothwell AL. Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study. Biological Psychiatry 2006, 61: 273-278. PMID: 16996487, DOI: 10.1016/j.biopsych.2006.06.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge of OnsetAntigens, CDAntigens, Differentiation, T-LymphocyteAutoantigensBlood Cell CountCD4 Lymphocyte CountCD8-Positive T-LymphocytesChildData Interpretation, StatisticalFemaleFlow CytometryHumansImmune ToleranceInterleukin-2 Receptor alpha SubunitLectins, C-TypeLymphocyte CountMaleStreptococcal InfectionsTic DisordersT-LymphocytesTourette SyndromeConceptsT reg cellsRegulatory T cellsReg cellsTourette syndromeT cellsTS patientsFluorescence-activated cell sortingHealthy age-matched control childrenHealthy age-matched control subjectsT reg cell numbersBeta-hemolytic streptococcal infectionAge-matched control subjectsHost T-cell immunityPathogenesis of TSHemolytic streptococcal infectionT cell immunitySignificant decreaseAge-matched control childrenAutoimmune inflammationCell immunityStreptococcal infectionAutoreactive lymphocytesImmune toleranceAutoimmune responsePeripheral bloodThe mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cells
Chae WJ, Henegariu O, Lee SK, Bothwell AL. The mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9631-9636. PMID: 16769892, PMCID: PMC1480458, DOI: 10.1073/pnas.0600225103.Peer-Reviewed Original ResearchConceptsWild-type FOXP3Regulatory T cellsCD4 T cellsT cellsAutoimmune diseasesTh2-type cytokine secretionScurfy mutant mouseSevere autoimmune diseaseFoxp3 transcription factorAntigenic stimulationCytokine secretionFoxp3Suppressive functionMutant miceAdhesion moleculesSuppressor activityDiseaseGlutamic acidImportant roleCellsCD103HyporesponsivenessTh1Leucine zipper domainTranscription factors
2004
Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residues
Chae WJ, Lee HK, Han JH, Kim SW, Bothwell AL, Morio T, Lee SK. Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residues. International Immunology 2004, 16: 1225-1236. PMID: 15302845, DOI: 10.1093/intimm/dxh120.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseTCR zeta chainTyrosine phosphorylated proteinsTyrosine residuesZeta chainPhosphorylated proteinsT cell activationCell deathFirst tyrosine residueCell activationInfluence of mutationsActivation-induced cell deathProtein kinaseDistinctive regulationIntracellular signalsDifferential regulationITAMMAPK phosphorylationTCR stimulationStepwise deletionJurkat transfectantsDistinct signalsActivation signalsMutationsResidues
2003
Immunopathology of human T cell responses to skin, artery and endothelial cell grafts in the human peripheral blood lymphocyte/severe combined immunodeficient mouse
Pober JS, Bothwell AL, Lorber MI, McNiff JM, Schechner JS, Tellides G. Immunopathology of human T cell responses to skin, artery and endothelial cell grafts in the human peripheral blood lymphocyte/severe combined immunodeficient mouse. Seminars In Immunopathology 2003, 25: 167-180. PMID: 12955465, DOI: 10.1007/s00281-003-0135-1.Peer-Reviewed Original ResearchConceptsLymphocytes/Peripheral blood lymphocyte/Human T cell responsesEndothelial cellsT cell responsesHuman peripheral bloodPig endotheliumHuman endothelial cellsPeripheral bloodCell graftsImmunodeficiency miceImmunodeficient miceCell responsesEndothelial liningRejection responseHuman vesselsBlood vesselsHuman arteriesLimited experienceTransplantationArteryImmunological propertiesSkinMiceHuman skin
2002
Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction
Shim JH, Lee HK, Chang EJ, Chae WJ, Han JH, Han DJ, Morio T, Yang JJ, Bothwell A, Lee SK. Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10617-10622. PMID: 12149481, PMCID: PMC124991, DOI: 10.1073/pnas.162522099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntifungal AgentsApoptosisCaspase 3Caspase 9CaspasesCell DivisionCyclosporineFuransHeart TransplantationHeLa CellsHumansImmunosuppressive AgentsJurkat CellsLipidsLymphocyte ActivationMolecular StructurePhosphorylationPoly(ADP-ribose) PolymerasesProto-Oncogene Proteins c-bcl-2RatsRats, Inbred LewRats, WistarReceptor-CD3 Complex, Antigen, T-CellSignal TransductionT-LymphocytesTyrosine
1996
Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells.
Maher SE, Karmann K, Min W, Hughes CC, Pober JS, Bothwell AL. Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells. The Journal Of Immunology 1996, 157: 3838-44. PMID: 8892613, DOI: 10.4049/jimmunol.157.9.3838.Peer-Reviewed Original ResearchAbataceptAmino Acid SequenceAnimalsAntigens, CDAntigens, DifferentiationAortaB7-2 AntigenBase SequenceCells, CulturedCHO CellsCloning, MolecularCricetinaeCricetulusCTLA-4 AntigenDNA, ComplementaryEndothelium, VascularHumansImmunoconjugatesInterleukin-2Lymphocyte ActivationMembrane GlycoproteinsMolecular Sequence DataSequence AlignmentSequence Homology, Amino AcidSpecies SpecificitySwineT-LymphocytesTransfectionUmbilical Veins