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
2017
Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis
Chae W, Park J, Henegariu O, Yilmaz S, Hao L, Bothwell ALM. Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis. Immunology 2017, 152: 265-275. PMID: 28556921, PMCID: PMC5588763, DOI: 10.1111/imm.12766.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesAutoimmunityCell MembraneCell ProliferationCHO CellsColitisColonCricetulusDisease Models, AnimalDNA-Binding ProteinsForkhead Transcription FactorsGenetic Predisposition to DiseaseIntercellular Signaling Peptides and ProteinsLymphocyte ActivationMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesPhenotypeSelf ToleranceSignal TransductionTime FactorsT-Lymphocytes, RegulatoryTransfectionConceptsRegulatory T cellsTreg cellsDKK-1 expressionAutoimmune colitisDickkopf-1T cellsT cell-mediated toleranceEffector CD4 T cellsCD4 T cellsInduction of toleranceT cell proliferationT cell receptor stimulationNovel TregColitis modelImmunological homeostasisImmunological toleranceFoxp3Receptor stimulationCanonical Wnt pathwayColitisFunctional inhibitionMonoclonal antibodiesDe novo protein synthesisProtein kinase pathwaySuppressor function
2016
Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen
Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen. Scientific Reports 2016, 6: 28495. PMID: 27335315, PMCID: PMC4917844, DOI: 10.1038/srep28495.Peer-Reviewed Original ResearchConceptsFollicular helper T cell responsesHelper T cell responsesT cell responsesCell responsesTfh cellsT cellsGC responseMale T cellsPeroxisome proliferator-activated receptor gammaTfh cell responsesEffector T cellsPPARγ agonist pioglitazoneProliferator-activated receptor gammaT cell regulationWild-type miceRole of PPARγGerminal center B cellsT cell activationGender-specific differencesTfh responsesAgonist pioglitazoneAutoimmune diseasesMenstrual cycleFemale miceMale mice
2014
PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation
Park HJ, Kim DH, Choi JY, Kim WJ, Kim JY, Senejani AG, Hwang SS, Kim LK, Tobiasova Z, Lee GR, Craft J, Bothwell AL, Choi JM. PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation. PLOS ONE 2014, 9: e99127. PMID: 24921943, PMCID: PMC4055678, DOI: 10.1371/journal.pone.0099127.Peer-Reviewed Original ResearchConceptsFollicular helper T cellsHelper T cellsT cellsGerminal center reactionTfh cellsSheep red blood cell immunizationRed blood cell immunizationCenter reactionPeroxisome proliferator-activated receptor gammaIL-21 expressionProliferator-activated receptor gammaWild-type T cellsType T cellsGerminal center formationGerminal center B cellsT cell activationCell immunizationAutoantibody productionGlomerular inflammationSignature cytokinesAdaptive immunityGerminal centersGlucose metabolismNF-κBB cells
2010
Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation
Choi JM, Shin JH, Sohn MH, Harding MJ, Park JH, Tobiasova Z, Kim DY, Maher SE, Chae WJ, Park SH, Lee CG, Lee SK, Bothwell AL. Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18575-18580. PMID: 20937878, PMCID: PMC2972952, DOI: 10.1073/pnas.1000400107.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsthmaAutoimmune DiseasesCell Membrane PermeabilityDisease Models, AnimalFemaleForkhead Transcription FactorsHumansInflammatory Bowel DiseasesLymphocyte ActivationMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsRecombinant Fusion ProteinsT-Lymphocytes, RegulatoryConceptsAllergic airway inflammationT cellsAirway inflammationAllergic diseasesFOXP3 proteinOvalbumin-induced allergic airway inflammationWild-type CD4 T cellsAllergic disease modelsDevelopment of colitisInflammatory bowel diseaseRegulatory T cellsCD4 T cellsInflammatory immune responseT cell activationFoxP3 transductionBowel diseaseScurfy miceTreg functionAutoimmune diseasesAutoimmune symptomsIntranasal deliveryTherapeutic effectImmune responseSystemic deliveryClinical potential
2009
Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation
Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G. Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation. Journal Of Experimental Medicine 2009, 206: 2407-2416. PMID: 19808254, PMCID: PMC2768861, DOI: 10.1084/jem.20082286.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCytokinesEncephalomyelitis, Autoimmune, ExperimentalGATA3 Transcription FactorInterleukin-6Lymphocyte ActivationMiceMice, KnockoutSTAT4 Transcription FactorSTAT6 Transcription FactorT-Box Domain ProteinsTh1 CellsTh2 CellsT-Lymphocytes, Helper-InducerTransforming Growth Factor betaConceptsTh17 cell differentiationTh17 cellsIL-6Wild-type BALB/c miceBALB/c miceTh17-specific transcription factorsExperimental autoimmune encephalomyelitisT helper cellsCell differentiationGrowth factor betaTh2 cell differentiationGrowth factor βC-STATAutoimmune encephalomyelitisAntiinflammatory cytokinesAutoimmune disordersProinflammatory cytokinesHelper cellsBeta antibodyC miceTh2 cellsFactor betaGATA-3CytokinesMice
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 activation
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 signalsMutationsResiduesEvidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase
Fernandez-Cabezudo MJ, Vijayasarathy C, Pflugh DL, Bothwell AL, al-Ramadi BK. Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase. International Immunology 2004, 16: 1215-1223. PMID: 15237112, DOI: 10.1093/intimm/dxh124.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteClone CellsHumansInterleukin-4Lectins, C-TypeLeukosialinLymphocyte ActivationLymphocyte Specific Protein Tyrosine Kinase p56(lck)MiceMultiprotein ComplexesPhosphoproteinsPhosphorylationReceptors, Interleukin-2Shc Signaling Adaptor ProteinsSialoglycoproteinsSignal TransductionSrc Homology 2 Domain-Containing, Transforming Protein 1Th2 CellsConceptsCD43 ligationSLP-76Adaptor protein SLP-76Tyrosine kinaseLck-deficient cellsTyrosine phosphorylated proteinsLck tyrosine kinaseMulti-component complexesT cell biologyNaive splenic T cellsPhosphorylated proteinsMajor protein bandsTyrosine phosphorylationCell biologyPathway componentsDifferential requirementExact functionDifferent effector functionsPhosphorylationT cell moleculesCellular proliferationProtein bandsCell moleculesLckKinase
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