2025
Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome
Shin J, Shin H, Gutierrez A, Yoo N, Par-Young J, Osmani L, Shin M, Sanchez-Lara P, Bucala R, Soffer G, Kang I. Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome. EBioMedicine 2025, 112: 105578. PMID: 39891996, PMCID: PMC11840234, DOI: 10.1016/j.ebiom.2025.105578.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsRecurrent sinopulmonary infectionsT cell functionRNA-seq analysisT cellsHealthy controlsSinopulmonary infectionsRNA-seqT-betIFN-gFrequency of CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cell functionTh1 transcription factor T-betDeletion syndromeFlow cytometryCompared to age-matched healthy controlsTranscription factor T-betDecreased T-betUrinary tract abnormalitiesAge-matched healthy controlsMultiplex assayDownstream effector cytokinesEffector cytokinesRecurrent infectionsTh17 cytokines
2023
Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice
Nickerson K, Smita S, Hoehn K, Marinov A, Thomas K, Kos J, Yang Y, Bastacky S, Watson C, Kleinstein S, Shlomchik M. Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice. Journal Of Experimental Medicine 2023, 220: e20221346. PMID: 36828389, PMCID: PMC9997508, DOI: 10.1084/jem.20221346.Peer-Reviewed Original Research
2020
Defining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysis
Shin M, Kim D, Park H, Dong X, Koumpouras F, Kang I. Defining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysis. The Journal Of Immunology 2020, 204: 154.19-154.19. DOI: 10.4049/jimmunol.204.supp.154.19.Peer-Reviewed Original ResearchHuman effector memory CD8EM CD8Effector memory CD8T cellsIL-7RαMemory CD8Cell subsetsIL-7 receptor alphaIL-7 receptor alpha chainT cell subsetsCo-stimulatory moleculesT cell heterogeneityHigh-dimensional single-cell analysisReceptor alpha chainLupus patientsImmune landscapeCell surface moleculesHeterogeneous cell subsetsT-betCD8Effector functionsDifferential expressionReceptor alphaSingle-cell RNA-seq analysisPathologic conditions
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, NeutralizingAntibody AffinityAntigens, CD19B-LymphocytesCytokinesFemaleGerminal CenterHIV InfectionsHumansImmunologic MemoryLymph NodesMaleMiddle AgedMutation RatePhenotypeReceptors, Antigen, B-CellT-Box Domain ProteinsT-Lymphocytes, Helper-InducerTranscriptomeYoung AdultConceptsHIV-specific B cellsT-betGC B cellsGerminal centersB cellsLymph nodesPoor affinity maturationChronic immune activationMemory B cell compartmentAntibody-mediated immunityChronic infectious diseaseOptimal antibody responseB cell compartmentChronic human infectionsB cell receptorHIV viremiaImmunologic outcomesHIV infectionViremic individualsChronic viremiaImmune activationPeripheral bloodProtective antibodiesAntibody responseCD19
2018
Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1.
DeLong JH, Hall AO, Konradt C, Coppock GM, Park J, Harms Pritchard G, Hunter CA. Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1. The Journal Of Immunology 2018, 200: 1761-1770. PMID: 29358280, PMCID: PMC5821564, DOI: 10.4049/jimmunol.1701154.Peer-Reviewed Original ResearchConceptsT cell expressionIL-27T cellsEffector cellsSca-1Cell expressionPathogen-specific T cellsMemory precursor effector cellsEndogenous IL-27Identification of CD8Type I IFNMemory stem cellsCytokine-mediated signalsEffector CD4Ly6C expressionSca-1 expressionImmune populationsT-betExpression of Ly6CMemory populationMouse CD4I IFNLy6CIFNMouse splenocytesActivation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice
Tan Q, Tai N, Li Y, Pearson J, Pennetti S, Zhou Z, Wong FS, Wen L. Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice. JCI Insight 2018, 3: e95882. PMID: 29321370, PMCID: PMC5821212, DOI: 10.1172/jci.insight.95882.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAutoantibodiesAutoimmunityB-LymphocytesCytidine DeaminaseCytokinesDiabetes Mellitus, Type 1Enzyme ActivationFemaleGene Knockdown TechniquesImmune ToleranceImmunoglobulin AImmunoglobulin GInsulinInterferon-gammaLymph NodesMaleMiceMice, Inbred NODMilkPlacentaPregnancySpleenT-LymphocytesVirulenceConceptsDiabetes developmentB cellsT cellsNOD miceActivation-induced cytidine deaminaseType 1 diabetes developmentAccelerated diabetes developmentAnti-insulin autoantibodiesIFN-γ expressionMore rapid onsetB cell interactionsRole of AIDAccelerated T1DActivation-induced cytidine deaminase (AID) deficiencyAutoimmune diabetesIslet autoimmunityT1D developmentImmune toleranceMaternal IgGT-betRapid onsetPresence of AIDMiceDeaminase deficiencyCD4
2017
STAT4 and T-bet control follicular helper T cell development in viral infections
Weinstein JS, Laidlaw BJ, Lu Y, Wang JK, Schulz VP, Li N, Herman EI, Kaech SM, Gallagher PG, Craft J. STAT4 and T-bet control follicular helper T cell development in viral infections. Journal Of Experimental Medicine 2017, 215: 337-355. PMID: 29212666, PMCID: PMC5748849, DOI: 10.1084/jem.20170457.Peer-Reviewed Original ResearchConceptsIL-21Tfh cellsT-betViral infectionFollicular helper T cellsHelper T cell developmentAcute viral infectionIFN-γ productionHelper T cellsGerminal center B cell survivalB cell survivalT cell developmentIL-4Viral challengeIL-9T cellsImmunoglobulin isotypesIFNSoluble factorsGC responseInfectionGC reactionSTAT4BCL6Cell survival
2015
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection
Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS, Kleinstein SH, Kaech SM. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. Journal Of Experimental Medicine 2015, 212: 2041-2056. PMID: 26503446, PMCID: PMC4647261, DOI: 10.1084/jem.20150186.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCluster AnalysisFlow CytometryHomeodomain ProteinsHost-Pathogen InteractionsLectins, C-TypeLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMice, Inbred C57BLMice, KnockoutMice, TransgenicOligonucleotide Array Sequence AnalysisProtein BindingReceptors, ImmunologicRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionT-Box Domain ProteinsT-Lymphocytes, CytotoxicTranscriptomeZinc Finger E-box Binding Homeobox 2ConceptsTerminal differentiationT cell terminal differentiationChromatin immunoprecipitation sequencingNovel genetic pathwaysTranscription factor ZEB2Cell terminal differentiationZeb2 functionImmunoprecipitation sequencingMemory cell potentialDifferentiation programGenetic pathwaysCytotoxic T lymphocyte differentiationTerminal effectorZEB2 mRNAPrecursor cellsCoordinated actionLymphocyte differentiationT lymphocyte differentiationMemory precursor cellsGenesT-betDifferentiationViral infectionZEB2CooperateChitinase like protein BRP-39 suppress Th1 differentiation via regulation of IFNγ-STAT1 axis (LYM8P.633)
Kim D, Park H, Lee J, Kang M, Lee C, Elias J, Choi J. Chitinase like protein BRP-39 suppress Th1 differentiation via regulation of IFNγ-STAT1 axis (LYM8P.633). The Journal Of Immunology 2015, 194: 201.9-201.9. DOI: 10.4049/jimmunol.194.supp.201.9.Peer-Reviewed Original ResearchT cell immunityBRP-39Th1 cellsT cellsTCR stimuliUp-regulate T-betExpression of PTPN2Naive CD4 T cellsIncreased production of IL-2Production of IL-2CD4 T cellsNaive T cellsT cell activationEnzyme sitesChitinase activityParasite life cycleAnti-parasite immune responsesSignaling pathwayRegulatory roleChitinaseTh2 cellsInnate immunityT-betTh1 differentiationIFN-g
2014
T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells
Fu J, Wu Y, Nguyen H, Heinrichs J, Schutt S, Liu C, Anasetti C, Yu X. T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease By Regulating Hematopoietic Antigen Presenting Cells. Blood 2014, 124: 846. DOI: 10.1182/blood.v124.21.846.846.Peer-Reviewed Original ResearchAntigen presenting cellsDonor T cellsT cell apoptosisAcute GVHDRecipient dendritic cellsDendritic cellsIFN-γ productionT-betT cellsWT T cellsT cell activationHost diseasePresenting cellsAllogeneic hematopoietic stem cell transplantationAPC functionAlloreactive donor T cellsDevelopment of aGVHDDonor T cell activationDonor T-cell responsesAllogeneic bone marrow transplantationHematopoietic stem cell transplantationTranscription factor T-betAcute Graft-VersusInduction of GVHDSevere acute GVHDCD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection
Laidlaw BJ, Zhang N, Marshall HD, Staron MM, Guan T, Hu Y, Cauley LS, Craft J, Kaech SM. CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection. Immunity 2014, 41: 633-645. PMID: 25308332, PMCID: PMC4324721, DOI: 10.1016/j.immuni.2014.09.007.Peer-Reviewed Original ResearchConceptsT cellsTRM cellsT-betTissue-resident memory T cellsLung-resident memory CD8T cell-dependent signalsT cell-derived interferonTranscription factor T-betLung Trm cellsMemory T cellsInfluenza viral infectionInfluenza virus infectionT cell helpHeterosubtypic challengeCD103 expressionMemory CD8Respiratory infectionsMucosal sitesCell helpAirway epitheliumVirus infectionViral infectionInfectionLung airwaysImpaired ability
2013
The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans
Lozano E, Joller N, Cao Y, Kuchroo VK, Hafler DA. The CD226/CD155 Interaction Regulates the Proinflammatory (Th1/Th17)/Anti-Inflammatory (Th2) Balance in Humans. The Journal Of Immunology 2013, 191: 3673-3680. PMID: 23980210, PMCID: PMC3819731, DOI: 10.4049/jimmunol.1300945.Peer-Reviewed Original ResearchConceptsNaive T cellsT cellsInflammatory balanceIL-13IL-17-producing cellsRole of CD226IL-17 productionIL-17 secretionHuman autoimmune diseasesIFN-γ productionIL-13 secretionIFN-γ expressionProduction of IFNSTAT-6 phosphorylationT cell activationHuman T cellsLigand CD155Th17 cellsIL-17Autoimmune diseasesIL-4T-betTh1 differentiationTh17 conditionsTherapeutic approachesGerminal Center Formation Controlled by Balancing Between Follicular Helper T Cells and Follicular Regulatory T Cells
Park H, Kim D, Choi J. Germinal Center Formation Controlled by Balancing Between Follicular Helper T Cells and Follicular Regulatory T Cells. Hanyang Medical Reviews 2013, 33: 10-16. DOI: 10.7599/hmr.2013.33.1.10.Peer-Reviewed Original ResearchFollicular helper T cellsFollicular regulatory T cellsGerminal center reactionRegulatory T cellsHelper T cellsT cell helpT cellsB cellsCenter reactionAutoimmune diseasesCell helpT-betBCL-6Antigen-specific T cellsTranscription factor Bcl-6Expression of CXCR5B cell folliclesPeripheral tolerance mechanismsCD4 T cellsMemory B cellsGerminal center formationIsotype class switchingTfh populationTh17 cellsTfh differentiation
2012
T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease Through Controlling T Cell Differentiation and Function
Fu J, Wang D, Yu Y, Kaosaard K, Liu C, Anasetti C, Yu X. T-Bet Is Critical for the Development of Acute Graft-Versus-Host Disease Through Controlling T Cell Differentiation and Function. Blood 2012, 120: 452. DOI: 10.1182/blood.v120.21.452.452.Peer-Reviewed Original ResearchDonor T cellsHematopoietic cell transplantationAllogeneic hematopoietic cell transplantationInduction of GVHDGVHD target organsT cell infiltrationCD4 T cellsTh17 cellsT-betT cellsAcute GVHDHost diseaseAdoptive transferTh1 cellsCell infiltrationMurine allogeneic bone marrow transplantation modelTarget organsAllogeneic bone marrow transplantation modelWT CD4 T cellsIFN-γ KO miceBALB/c miceLess body weight lossTranscription factor T-betT-box transcription factor T-betAcute Graft-VersusThe TIGIT/CD226 Axis Regulates Human T Cell Function
Lozano E, Dominguez-Villar M, Kuchroo V, Hafler DA. The TIGIT/CD226 Axis Regulates Human T Cell Function. The Journal Of Immunology 2012, 188: 3869-3875. PMID: 22427644, PMCID: PMC3324669, DOI: 10.4049/jimmunol.1103627.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteCD4-Positive T-LymphocytesCell CommunicationCell ProliferationCells, CulturedCytokinesDendritic CellsGATA3 Transcription FactorGene Expression RegulationHumansImmune ToleranceReceptors, ImmunologicReceptors, VirusRNA, Small InterferingSignal TransductionT-Box Domain ProteinsConceptsT cell functionT cellsAutoimmune diseasesT-betTIGIT/CD226 axisHuman T cell responsesT cell-intrinsic mannerHuman T cell functionAlternative costimulatory pathwaysT cell responsesCell functionDendritic cell surfaceHuman autoimmune diseasesIL-10 expressionT cell IgIFN regulatory factor 4T cell proliferationOrphan receptor CDirect inhibitory effectIFN-γ mRNACell-intrinsic mannerRegulatory factor 4TIGIT expressionTIGIT knockdownTolerogenic phenotype
2011
Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice
Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu X. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011, 118: 5011-5020. PMID: 21856864, PMCID: PMC3208306, DOI: 10.1182/blood-2011-03-340315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCells, CulturedCombined Modality TherapyGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationLeukemiaMiceMice, Inbred C57BLMice, KnockoutMolecular Targeted TherapyNuclear Receptor Subfamily 1, Group F, Member 3T-Box Domain ProteinsTh1 CellsTh17 CellsTransplantation, HomologousConceptsHematopoietic cell transplantationGVL effectT-betT cellsTranscription factor T-betPrevention of GVHDDonor T cellsCD8 T cellsAmeliorated GVHDGVL activityNaive ThTh17 subsetAdoptive transferCell transplantationTh17 differentiationEffective therapyHematologic malignanciesAllogeneic hostsGVHDMajor MHCTh1Regulatory phenotypeSkewed differentiationTargeted disruptionRORγt
2010
Transgenic modelling of cytokine polarization in the lung
Dela Cruz CS, Kang M, Cho W, Lee CG. Transgenic modelling of cytokine polarization in the lung. Immunology 2010, 132: 9-17. PMID: 21091906, PMCID: PMC3015070, DOI: 10.1111/j.1365-2567.2010.03376.x.Peer-Reviewed Original ResearchConceptsCytokine polarizationT helper type 17 cytokinesT helper type 2T helper type 1Type 1Type 17 cytokinesHelper type 2Type 2 cytokinesHelper type 1Human lung diseasesVariety of cytokinesCytokine milieuPulmonary inflammationEnvironmental allergensLung diseaseTissue phenotypeInjury modelT-betCommon siteCertain cytokinesEffector functionsTransgenic miceIndividual cytokinesPathophysiological consequencesType 2T-bet, GATA-3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species
Díaz YR, Rojas R, Valderrama L, Saravia NG. T-bet, GATA-3, and Foxp3 Expression and Th1/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species. The Journal Of Infectious Diseases 2010, 202: 406-415. PMID: 20583921, PMCID: PMC4850829, DOI: 10.1086/653829.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsCoculture TechniquesCytokinesFemaleForkhead Transcription FactorsGATA3 Transcription FactorGene ExpressionGene Expression ProfilingHumansLeishmaniaLeishmaniasisLeukocytes, MononuclearMaleMiddle AgedT-Box Domain ProteinsTh1 CellsTh2 CellsTreatment OutcomeYoung AdultConceptsGATA-3 expressionT cell differentiationTumor necrosis factor alphaT-bet expressionNecrosis factor alphaT-betHuman infectionsGATA-3Th2 responsesAsymptomatic infectionFactor alphaInterleukin-4Cutaneous leishmaniasisInterferon gammaTh1/Th2 cytokine productionTh1/Th2 cytokine responseHigher T-bet expressionTh1/Th2 responseActive recurrent diseaseRecurrent cutaneous leishmaniasisTh2 cytokine responsesExperimental cutaneous leishmaniasisProinflammatory cytokine interferon-gammaInterleukin-10 secretionTh2 cytokine productionIL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9)
Dominguez-Villar M, Hafler D, Baecher-Allan C. IL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9). The Journal Of Immunology 2010, 184: 138.9-138.9. DOI: 10.4049/jimmunol.184.supp.138.9.Peer-Reviewed Original ResearchRegulatory T cellsT cellsEffector phenotypeTreg functionIL-10Immune responseHuman Treg functionCD4 T cellsT cell responsesIL-12 familyIL-12 inducesTreg suppressionPeripheral toleranceCytokine milieuT-betIFN-gammaTregsImmune systemCell responsesCytokinesRecent evidencePivotal roleCellsPhenotypeDistinct effects
2009
T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow
Jenne CN, Enders A, Rivera R, Watson SR, Bankovich AJ, Pereira JP, Xu Y, Roots CM, Beilke JN, Banerjee A, Reiner SL, Miller SA, Weinmann AS, Goodnow CC, Lanier LL, Cyster JG, Chun J. T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. Journal Of Experimental Medicine 2009, 206: 2469-2481. PMID: 19808259, PMCID: PMC2768857, DOI: 10.1084/jem.20090525.Peer-Reviewed Original Research
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