2015
Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells
Hernandez AL, Kitz A, Wu C, Lowther DE, Rodriguez DM, Vudattu N, Deng S, Herold KC, Kuchroo VK, Kleinewietfeld M, Hafler DA. Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. Journal Of Clinical Investigation 2015, 125: 4212-4222. PMID: 26524592, PMCID: PMC4639983, DOI: 10.1172/jci81151.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, NeutralizingAutoimmunityCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesColitisCytokinesForkhead Transcription FactorsGene Expression ProfilingGenes, ReporterGraft vs Host DiseaseHeterograftsHumansImmediate-Early ProteinsInflammationInterferon-gammaLeukocytes, MononuclearMaleMiceProtein Serine-Threonine KinasesRNA InterferenceRNA, Small InterferingSodium ChlorideSodium Chloride, DietaryT-Lymphocytes, RegulatoryConceptsHigh-salt dietTreg functionIFNγ secretionCD4 effector cellsHuman Treg functionRegulatory T cellsAdoptive transfer modelAnti-IFNγ antibodyHost disease modelType 1 diabetesInduction of proinflammatoryTreg pathwayExperimental colitisXenogeneic graftEffector cellsMultiple sclerosisProinflammatory responseT cellsTregsMurine modelSuppressive activitySuppressive functionSerum/glucocorticoid-regulated kinaseAutoimmunityGlucocorticoid-regulated kinase
2014
CD45 ligation expands Tregs by promoting interactions with DCs
Camirand G, Wang Y, Lu Y, Wan YY, Lin Y, Deng S, Guz G, Perkins DL, Finn PW, Farber DL, Flavell RA, Shlomchik WD, Lakkis FG, Rudd CE, Rothstein DM. CD45 ligation expands Tregs by promoting interactions with DCs. Journal Of Clinical Investigation 2014, 124: 4603-4613. PMID: 25202978, PMCID: PMC4191025, DOI: 10.1172/jci74087.Peer-Reviewed Original ResearchConceptsT cellsTreg proliferationTreg expansionVivo expansionRegulatory T cellsConventional T cellsTransfer of TregsActivated T cellsTreg numbersTreg populationImmune toleranceHomeostatic proliferationWT miceExogenous antigensPeripheral homeostasisTregsImmune responseTherapeutic useCD45 ligationNuclear factorIntegrin-dependent mannerNuclear translocationLigationAntigenProliferationHumanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy
Vudattu NK, Waldron-Lynch F, Truman LA, Deng S, Preston-Hurlburt P, Torres R, Raycroft MT, Mamula MJ, Herold KC. Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy. The Journal Of Immunology 2014, 193: 587-596. PMID: 24943216, PMCID: PMC4123131, DOI: 10.4049/jimmunol.1302455.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal GlandsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAutoimmune DiseasesCytokinesDisease Models, AnimalFlow CytometryHumansInterleukin Receptor Common gamma SubunitIpilimumabLiverLymphocyte ActivationMacrophagesMiceMice, Inbred NODMice, KnockoutMice, SCIDPhosphorylationSTAT5 Transcription FactorStem Cell TransplantationSurvival AnalysisT-LymphocytesT-Lymphocytes, RegulatoryTransplantation, HeterologousWeight LossConceptsAnti-nuclear AbsAutoimmune diseasesRegulatory cellsHumanized miceT cellsImmune responseWeight lossMesenteric lymph nodesHuman autoimmune diseasesInduction of autoimmunityT-cell immunotherapyRelease of IFNHuman immune responseImmune-deficient miceIpilimumab treatmentInflammatory sequelaeLymph nodesCell immunotherapyIP-10Macrophage infiltrationCytokine productionSpleen cellsPathologic processesHepatitisMice
2013
Transplant Tolerance to Pancreatic Islets Is Initiated in the Graft and Sustained in the Spleen
Gagliani N, Jofra T, Valle A, Stabilini A, Morsiani C, Gregori S, Deng S, Rothstein DM, Atkinson M, Kamanaka M, Flavell RA, Roncarolo MG, Battaglia M. Transplant Tolerance to Pancreatic Islets Is Initiated in the Graft and Sustained in the Spleen. American Journal Of Transplantation 2013, 13: 1963-1975. PMID: 23834659, PMCID: PMC3869180, DOI: 10.1111/ajt.12333.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, MonoclonalCD4 AntigensCD4-Positive T-LymphocytesForkhead Transcription FactorsGraft SurvivalIslets of LangerhansIslets of Langerhans TransplantationLeukocyte Common AntigensMiceMice, Inbred BALB CMice, Inbred C57BLSpleenT-Lymphocytes, RegulatoryTransplantation ToleranceTransplantation, HomologousConceptsTr1 cellsLong-term toleranceTransplant toleranceRegulatory type 1 (Tr1) cellsSpecific immunomodulatory treatmentTreg cell transferCD25- T cellsRegulatory cell typesType 1 cellsAllograft toleranceImmunomodulatory treatmentTreg cellsAllogeneic transplantationT cellsMouse modelImmune systemTregsPancreatic isletsSpleenAllograftsCell typesCellsRegulatory functionsTransplantationEngraftment
2012
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells
2011
Regulatory T Cells Require Mammalian Target of Rapamycin Signaling To Maintain Both Homeostasis and Alloantigen-Driven Proliferation in Lymphocyte-Replete Mice
Wang Y, Camirand G, Lin Y, Froicu M, Deng S, Shlomchik WD, Lakkis FG, Rothstein DM. Regulatory T Cells Require Mammalian Target of Rapamycin Signaling To Maintain Both Homeostasis and Alloantigen-Driven Proliferation in Lymphocyte-Replete Mice. The Journal Of Immunology 2011, 186: 2809-2818. PMID: 21270412, PMCID: PMC5584652, DOI: 10.4049/jimmunol.0903805.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCell SurvivalGene Knock-In TechniquesHomeostasisIsoantigensLymphocyte ActivationLymphocyte CountLymphocyte DepletionLymphoid TissueMiceMice, Inbred BALB CMice, Inbred C57BLSignal TransductionSirolimusSkin TransplantationT-Lymphocytes, RegulatoryTOR Serine-Threonine KinasesConceptsPercent of TregRegulatory T cellsHost disease modelT cellsTolerogenic agentsMammalian targetConversion of TregsEffect of RapaFoxp3(-) T cellsNumber of TregsSolid organ transplantationDisease modelsAlloantigen-induced proliferationWild-type miceRAPA therapyTreg depletionTreg survivalCD4 cellsLymphopenic hostsImmunosuppressive drugsTregsOrgan transplantationAnimal modelsBaseline numberTconv
2005
Testicular Immune Privilege Promotes Transplantation Tolerance by Altering the Balance between Memory and Regulatory T Cells
Nasr IW, Wang Y, Gao G, Deng S, Diggs L, Rothstein DM, Tellides G, Lakkis FG, Dai Z. Testicular Immune Privilege Promotes Transplantation Tolerance by Altering the Balance between Memory and Regulatory T Cells. The Journal Of Immunology 2005, 174: 6161-6168. PMID: 15879112, DOI: 10.4049/jimmunol.174.10.6161.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BlockingApoptosisCD40 AntigensCD40 LigandCD8-Positive T-LymphocytesEpitopes, T-LymphocyteGraft RejectionGrowth InhibitorsImmunologic MemoryIslets of Langerhans TransplantationLymphocyte ActivationLymphocyte CountMaleMiceMice, Inbred BALB CMice, Inbred C3HMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, Interleukin-2TestisT-Lymphocytes, RegulatoryTransplantation ToleranceTransplantation, HeterotopicConceptsRegulatory T cellsNon-privileged sitesIslet allograftsTransplantation toleranceT cellsImmune privilegeCD40/CD40L costimulationIntratesticular islet allograftsIslet allograft toleranceAcute allograft rejectionProlong allograft survivalLate allograft failureTesticular immune privilegePrivileged siteAllograft failureAllograft survivalAllograft toleranceCostimulatory blockadeAllograft rejectionAlloimmune responseSkin allograftsIslet transplantationImmune regulationImmune responseAllografts