2023
IL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal
Pierce C, Loh L, Steach H, Cheshenko N, Preston-Hurlburt P, Zhang F, Stransky S, Kravets L, Sidoli S, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal. Journal Of Clinical Investigation 2023, 133: e164317. PMID: 37079384, PMCID: PMC10232005, DOI: 10.1172/jci164317.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV latency reversalT cellsLatency reversalHuman CD4HIV-1 viral loadHIV-1 restriction factorsHSV-2 recurrencesHSV-2 infectionHIV-1 latencyUpregulation of MALAT1Primary human CD4HSV-2 proteinsViral loadHIV replicationPeripheral bloodMALAT1 expressionHSV-2Tissue reservoirsCD4Viral replicationExpression of transcriptsBystander cellsRestriction factorsMALAT1
2020
T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation
Yan J, Pandey SP, Barnes BJ, Turner JR, Abraham C. T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation. Cell Reports 2020, 31: 107820. PMID: 32610123, PMCID: PMC7409536, DOI: 10.1016/j.celrep.2020.107820.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCell DifferentiationCell MovementColitisCytokinesGenetic Predisposition to DiseaseHumansInflammationInterferon Regulatory FactorsIntestinesLymph NodesMice, Inbred BALB CReceptors, Antigen, T-CellReceptors, ChemokineSignal TransductionT-LymphocytesUp-RegulationConceptsInflammatory outcomesTh17-associated transcription factorsMultiple immune-mediated diseasesPromotes Intestinal InflammationTh17-associated cytokinesAnti-inflammatory cytokinesImmune-mediated diseasesTh2-associated cytokinesChemokine-induced migrationExperimental colitisIntestinal inflammationUlcerative colitisHuman CD4IRF5 polymorphismsT cell signalingCytokinesCD4IRF5Th1Myeloid lineageGenetic carriersColitisCell migrationKey roleOutcomes
2017
Human CD39+ Treg Cells Express Th17-Associated Surface Markers and Suppress IL-17 via a Stat3-Dependent Mechanism
Magid-Bernstein JR, Rohowsky-Kochan CM. Human CD39+ Treg Cells Express Th17-Associated Surface Markers and Suppress IL-17 via a Stat3-Dependent Mechanism. Journal Of Interferon & Cytokine Research 2017, 37: 153-164. PMID: 28387597, PMCID: PMC6435349, DOI: 10.1089/jir.2016.0071.Peer-Reviewed Original ResearchConceptsIL-17STAT3-dependent mechanismIL-23RHuman CD4T effector cellsIFN-γ productionEctonucleotidase CD39Autologous CD4Regulatory cellsAutoimmune responseEffector cellsAutoimmune diseasesTranscription factor STAT3Immune responseProliferative responseCD25CD4CD39Human CD39Surface markersSTAT3 activationCCR6STAT3CellsFirst evidence
2014
TLR7 induces anergy in human CD4+ T cells
Dominguez-Villar M, Gautron AS, de Marcken M, Keller MJ, Hafler DA. TLR7 induces anergy in human CD4+ T cells. Nature Immunology 2014, 16: 118-128. PMID: 25401424, PMCID: PMC4413902, DOI: 10.1038/ni.3036.Peer-Reviewed Original Research
2013
Studying the Role for CD4+ T Cell Subsets in Human Lupus
Kang I. Studying the Role for CD4+ T Cell Subsets in Human Lupus. 2013 DOI: 10.21236/ada585488.Peer-Reviewed Original ResearchIL-27IL-1Autoimmune complexesTh17 cellsLupus patientsPro-inflammatory cytokines IL-1Human monocytesExogenous IL-27IL-17 productionTh cell responsesT cell subsetsToll-like receptorsProduction of cytokinesIL-27 geneCytokines IL-1IL-1 expressionPotential therapeutic implicationsIL-10Human lupusCell subsetsPolarizing cytokinesT cellsHuman CD4Therapeutic implicationsPatients
2011
Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism
Jiang C, Parrish N, Wilen C, Li H, Chen Y, Pavlicek J, Berg A, Lu X, Song H, Tilton J, Pfaff J, Henning E, Decker J, Moody M, Drinker M, Schutte R, Freel S, Tomaras G, Nedellec R, Mosier D, Haynes B, Shaw G, Hahn B, Doms R, Gao F. Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism. Journal Of Virology 2011, 85: 10669-10681. PMID: 21835785, PMCID: PMC3187499, DOI: 10.1128/jvi.05249-11.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SubstitutionApelin ReceptorsCD4-Positive T-LymphocytesCells, Culturedenv Gene Products, Human Immunodeficiency VirusGene ExpressionHIV-1HumansMacrophagesReceptors, Formyl PeptideReceptors, G-Protein-CoupledReceptors, HIVReceptors, LipoxinReceptors, PeptideViral TropismConceptsF virusesHuman immunodeficiency virus type 1Immunodeficiency virus type 1Alternative coreceptor GPR15Sequential plasma samplesHuman immunodeficiency virusClade B virusesVirus type 1Cell linesPrimary human CD4Third variable loopEarly time pointsCoreceptor tropismFounder virusesMultiple CD4Immunodeficiency virusAlternative coreceptorsCCR5 coreceptorPrimary infectionB virusCXCR4 coreceptorFPRL-1T cellsHuman CD4Homozygous donorsInflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses
Sarin R, Wu X, Abraham C. Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 9560-9565. PMID: 21606346, PMCID: PMC3111257, DOI: 10.1073/pnas.1017854108.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCells, CulturedFlow CytometryHEK293 CellsHeLa CellsHumansImmunoblottingInflammatory Bowel DiseasesInterferon-gammaInterleukin-17Interleukin-23InterleukinsLuciferasesPolymorphism, Single NucleotideReceptors, InterleukinSignal TransductionSTAT3 Transcription FactorTh17 CellsConceptsT cellsIL-22 productionIL-23 receptorT cell functional responsesMultiple inflammatory diseasesPrimary human CD4WT CD8Tc17 cellsIL-17Arginine alleleInflammatory diseasesReceptor polymorphismsPrimary CD4Transcription 3 (STAT3) activationCD8Human CD4Function alterationsSignificant protectionHuman genetic polymorphismsGenetic polymorphismsR381QCD4AutoimmunityFunctional consequencesSignal transducerEngineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases
Wilen CB, Wang J, Tilton JC, Miller JC, Kim KA, Rebar EJ, Sherrill-Mix SA, Patro SC, Secreto AJ, Jordan AP, Lee G, Kahn J, Aye PP, Bunnell BA, Lackner AA, Hoxie JA, Danet-Desnoyers GA, Bushman FD, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases. PLOS Pathogens 2011, 7: e1002020. PMID: 21533216, PMCID: PMC3077364, DOI: 10.1371/journal.ppat.1002020.Peer-Reviewed Original ResearchConceptsT cellsHIV-1Human CD4X4-tropic HIV-1X4 HIV-1CCR5-tropic virusHumanized mouse modelLoss of CXCR4CXCR4-tropic HIVHIV-1 entryHuman T cellsCCR5Δ32 polymorphismAdoptive transferAutologous transplantCell surface expressionCXCR4 coreceptorMouse modelCD4CCR5CXCR4Surface expressionHIVInfectionSuch cellsHost cells
2010
1,25-dihyroxyvitamin D3 enhances the activity of the FOXP3 gene in human CD4+ T cells through directly binding to putative VDRE sites in the FOXP3 gene (49.2)
Kang I, Kim S, Lee W, Kang S, Lee J. 1,25-dihyroxyvitamin D3 enhances the activity of the FOXP3 gene in human CD4+ T cells through directly binding to putative VDRE sites in the FOXP3 gene (49.2). The Journal Of Immunology 2010, 184: 49.2-49.2. DOI: 10.4049/jimmunol.184.supp.49.2.Peer-Reviewed Original ResearchVitamin D receptorFOXP3 geneT cellsHuman CD4Dihyroxyvitamin D3Retinoid X receptorCNS regionsPresence of VDRFoxp3 promoter activityHuman FOXP3 geneImmune regulatory effectsFoxp3 gene expressionFOXP3 gene promoterBinding of VDRD receptorCD4X receptorPromoter activityResponse element siteRegulatory effectsVDREPutative response elementsReceptorsD3Response element
2009
TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines
Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. European Journal Of Immunology 2009, 39: 2492-2501. PMID: 19676072, PMCID: PMC2759376, DOI: 10.1002/eji.200939274.Peer-Reviewed Original ResearchCathepsin S Regulates Class II MHC Processing in Human CD4+ HLA-DR+ T Cells
Costantino CM, Ploegh HL, Hafler DA. Cathepsin S Regulates Class II MHC Processing in Human CD4+ HLA-DR+ T Cells. The Journal Of Immunology 2009, 183: 945-952. PMID: 19553543, PMCID: PMC2752291, DOI: 10.4049/jimmunol.0900921.Peer-Reviewed Original ResearchConceptsT cellsCathepsin S expressionSelf-Ag presentationClass II MHC moleculesClass II MHCT cell clonesCathepsin SII MHC moleculesCLIP expressionProfessional APCsConsequence of activationII MHCHuman CD4Presentation pathwayB cellsMHC moleculesEx vivoHLACell clonesInvariant chain proteolysisLysosomal proteasesS expressionCellsActivationCell surface
2004
PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells
Cai G, Karni A, Oliveira EM, Weiner HL, Hafler DA, Freeman GJ. PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells. Cellular Immunology 2004, 230: 89-98. PMID: 15598424, DOI: 10.1016/j.cellimm.2004.09.004.Peer-Reviewed Original ResearchConceptsPD-1 ligand blockadeT cellsPD-L1Myelin basic proteinPD-L2Human CD4Ex vivo dendritic cellsVivo dendritic cellsPD-1 ligandsPD-1 pathwayPrimary responseActivation of naïveNaive T cellsPD-1Dendritic cellsCytokine productionNormal donorsIFN-gammaSecondary responseCD4BlockadeHigh expressionNegative regulatory pathwaysInduced activationBasic proteinDefective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II
Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM. Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II. Journal Of Experimental Medicine 2004, 199: 1285-1291. PMID: 15117972, PMCID: PMC2211900, DOI: 10.1084/jem.20032158.Peer-Reviewed Original ResearchConceptsAutoimmune polyglandular syndromeRegulatory T cellsAPS IIT cellsAutoimmune polyglandular syndrome type IIOrgan-specific autoimmune diseasesAPS type IAPS type IIDefective suppressor functionNormal healthy donorsImportant surface markerPolyglandular syndromeAutoimmune endocrinopathiesControl patientsMultiple endocrinopathiesAutoimmune diseasesPeripheral bloodSuppressive capacityType IIHealthy donorsHuman autoimmunityCentral toleranceHuman CD4Murine modelSurface markersLoss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis. Journal Of Experimental Medicine 2004, 199: 971-979. PMID: 15067033, PMCID: PMC2211881, DOI: 10.1084/jem.20031579.Peer-Reviewed Original ResearchConceptsRegulatory T cellsMultiple sclerosisT cellsRegulatory T cell functionActivity of murineSpontaneous autoimmune diseaseT cell functionSingle cell cloning experimentsPeripheral toleranceCell cloning experimentsAutoimmune diseasesPeripheral bloodInflammatory diseasesHealthy donorsHuman CD4Effector functionsNormal controlsPatientsFunctional suppressionCell functionSignificant decreaseSclerosisProtein peptidesDiseaseActive suppression
1996
Endothelial cells augment the expression of CD40 ligand on newly activated human CD4+ T cells through a CD2/LFA‐3 signaling pathway
Karmann K, Hughes C, Fanslow W, Pober J. Endothelial cells augment the expression of CD40 ligand on newly activated human CD4+ T cells through a CD2/LFA‐3 signaling pathway. European Journal Of Immunology 1996, 26: 610-617. PMID: 8605928, DOI: 10.1002/eji.1830260316.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, Differentiation, T-LymphocyteB-LymphocytesCD2 AntigensCD40 LigandCD4-Positive T-LymphocytesCD58 AntigensCell AdhesionCell CommunicationCells, CulturedEndothelium, VascularHumansInterleukin-2LigandsLymphocyte ActivationMembrane GlycoproteinsPhytohemagglutininsSignal TransductionUp-RegulationConceptsCD40 ligand expressionExogenous IL-2T cellsIL-2Ligand expressionCD2/LFACD40 ligandHuman peripheral blood CD4Peripheral blood adherent cellsHelper T cell subsetsPeripheral blood T cellsPeripheral blood CD4T cell subsetsCo-stimulatory moleculesBlood T cellsHelper T cellsIL-2 receptorCo-stimulatory signalsIL-2 secretionInterleukin-2 secretionBlood CD4Endothelial effectsCell subsetsHuman CD4B cells
1995
PEC‐A: An immortalized porcine aortic endothelial cell
Khodadoust M, Candal F, Maher S, Murray A, Pober J, Davis W, Ades E, Bothwell A. PEC‐A: An immortalized porcine aortic endothelial cell. Xenotransplantation 1995, 2: 79-87. DOI: 10.1111/j.1399-3089.1995.tb00070.x.Peer-Reviewed Original ResearchAortic endothelial cellsCultured porcine aortic endotheliumNormal aortic endothelial cellsSignificant T-cell proliferative responsesMHC class II antigensT cell proliferative responsesEndothelial cellsClass IPorcine aortic endotheliumClass II antigensClass II expressionImmortalized porcine aortic endothelial cellsExpression of CD44Porcine aortic endothelial cellsCell surface antigensVon Willebrand factorPorcine ECII antigensT cellsProliferative responseHuman CD4Aortic endotheliumSurface antigenEndothelial responseAcetylated LDL
1994
Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage.
Paterson RK, Burkly LC, Kurahara DK, Dunlap A, Flavell RA, Finkel TH. Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage. The Journal Of Immunology 1994, 153: 3491-503. PMID: 7930572, DOI: 10.4049/jimmunol.153.8.3491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4 AntigensCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansMaleMiceMice, Inbred C57BLMice, TransgenicReceptors, Antigen, T-CellSelection, GeneticStochastic ProcessesThymus GlandT-Lymphocyte SubsetsPorcine aortic endothelial cells activate human T cells: Direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28
Murray A, Khodedoust M, Pober J, Bothwell A. Porcine aortic endothelial cells activate human T cells: Direct presentation of MHC antigens and costimulation by ligands for human CD2 and CD28. Immunity 1994, 1: 57-63. PMID: 7889399, DOI: 10.1016/1074-7613(94)90009-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigens, HeterophileCD2 AntigensCD28 AntigensCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedEndothelium, VascularHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansIn Vitro TechniquesLigandsLymphocyte ActivationSpecies SpecificitySwineT-LymphocytesConceptsPorcine aortic endothelial cellsHuman umbilical vein endothelial cellsHuman T cellsCTLA-4-IgT cellsAortic endothelial cellsEndothelial cellsCultured porcine aortic endothelial cellsMHC class II moleculesClass II moleculesMHC class IUmbilical vein endothelial cellsVein endothelial cellsAllogeneic responseMHC antigensHuman CD8CD28 pathwayCD8 moleculesHuman CD4Species-specific monoclonal antibodiesCD2 pathwayMonoclonal antibodiesClass IDirect presentationCD4
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