2023
Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.
Song W, Sanchez G, Mayer D, Blackburn H, Chernova I, Flavell R, Weinstein J, Craft J. Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection. The Journal Of Immunology 2023, 210: 1861-1865. PMID: 37133336, PMCID: PMC10247523, DOI: 10.4049/jimmunol.2300027.Peer-Reviewed Original ResearchConceptsAge-associated B cellsIL-21Acute lymphocytic choriomeningitis virus infectionB cellsLymphocytic choriomeningitis virus infectionB cell activationHumoral immunityLymphoid organsVirus infectionMouse modelViral infectionB cell developmentCell activationLymphotoxin αVivo generationTissue-specific signalsInfectionDe novo generationOrgan contributionIFNTissue microenvironmentCell developmentLiverPivotal contributorStage-specific roles
2022
Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection
Zander R, Kasmani MY, Chen Y, Topchyan P, Shen J, Zheng S, Burns R, Ingram J, Cui C, Joshi N, Craft J, Zajac A, Cui W. Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection. Immunity 2022, 55: 475-493.e5. PMID: 35216666, PMCID: PMC8916994, DOI: 10.1016/j.immuni.2022.01.018.Peer-Reviewed Original ResearchConceptsChronic viral infectionsIL-21Cell responsesViral infectionMixed bone marrow chimera experimentsBone marrow chimera experimentsMemory-like subsetTfh cell responsesCell-mediated immunityTfh cellsEffector CD8LCMV infectionHelper subsetsInterleukin-21Th1 cellsViral controlCD8Chimera experimentsCD4InfectionCell differentiationCellsSubsetResponseDistinct populationsHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19PatientsDevelopment of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers
Song W, Antao OQ, Condiff E, Sanchez GM, Chernova I, Zembrzuski K, Steach H, Rubtsova K, Angeletti D, Lemenze A, Laidlaw BJ, Craft J, Weinstein JS. Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers. Immunity 2022, 55: 290-307.e5. PMID: 35090581, PMCID: PMC8965751, DOI: 10.1016/j.immuni.2022.01.002.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsMemory subsetsRobust recall responsesB cell subsetsGerminal center formationB cell generationAcute infectionCell subsetsRecall responsesTh1 cellsProximal deliveryCD11cGerminal centersIntegrin LFA-1Viral infectionAntibody productionVLA-4Splenic retentionLFA-1TbetBCL6 expressionInfection
2021
T Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses
Lu Y, Craft J. T Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses. Frontiers In Immunology 2021, 12: 679909. PMID: 34177925, PMCID: PMC8222975, DOI: 10.3389/fimmu.2021.679909.Peer-Reviewed Original ResearchConceptsTfr cellsTreg cellsHumoral immunityGerminal centersAntigen-specific B cell responsesFollicular helper cellsFollicular regulatory (Tfr) cellsB cell folliclesRegulatory T cellsB cell autoreactivityB cell responsesGerminal center responseB cell toleranceVaccine design strategiesTranscription factor Bcl6Regulatory cellsHelper cellsImmune homeostasisProductive immunityT cellsViral infectionCenter responseCell responsesGC responseImmune challenge
2018
Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection
Xin G, Zander R, Schauder DM, Chen Y, Weinstein JS, Drobyski WR, Tarakanova V, Craft J, Cui W. Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection. Nature Communications 2018, 9: 5037. PMID: 30487586, PMCID: PMC6261948, DOI: 10.1038/s41467-018-07492-4.Peer-Reviewed Original ResearchConceptsCD4 T cellsIL-10Humoral immunityT cellsTfh cellsIL-10-expressing CD4 T cellsViral infectionAntiviral T cell responsesAcute LCMV infectionDouble reporter miceChronic viral infectionsCytokine IL-10T cell responsesPersistent viral infectionIL-10 signalingGerminal center reactionSingle-cell RNA-sequencing approachLCMV infectionHelper subsetsTh1 cellsChronic infectionInflammatory functionsViral controlPersistent infectionCell responses
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
A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control
Xin G, Schauder DM, Lainez B, Weinstein JS, Dai Z, Chen Y, Esplugues E, Wen R, Wang D, Parish IA, Zajac AJ, Craft J, Cui W. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control. Cell Reports 2015, 13: 1118-1124. PMID: 26527008, PMCID: PMC4859432, DOI: 10.1016/j.celrep.2015.09.069.Peer-Reviewed Original ResearchConceptsCD8 T cellsChronic viral infectionsBATF expressionT cellsIL-21Chronic infectionEffector functionsViral infectionCD8 T cell effector functionsAnti-viral effector functionsCD8 T cell responsesCD8 T cell immunityT cell effector functionT cell immunityCD4 T cellsT cell responsesCell effector functionsT cell persistenceT cell maintenanceBlimp-1 expressionCD8 responsesCD4 helpCell immunityViral controlTranscription factor expressionThe Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells
Ray JP, Staron MM, Shyer JA, Ho PC, Marshall HD, Gray SM, Laidlaw BJ, Araki K, Ahmed R, Kaech SM, Craft J. The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells. Immunity 2015, 43: 690-702. PMID: 26410627, PMCID: PMC4618086, DOI: 10.1016/j.immuni.2015.08.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCalcium SignalingCell CycleCell DivisionEnzyme ActivationGlucoseGlycolysisInterleukin-2Interleukin-2 Receptor alpha SubunitLymphocytic choriomeningitis virusMechanistic Target of Rapamycin Complex 1Mice, Inbred C57BLMultiprotein ComplexesNFATC Transcription FactorsOxygen ConsumptionPositive Regulatory Domain I-Binding Factor 1Proto-Oncogene Proteins c-aktSignal TransductionSpecific Pathogen-Free OrganismsTh1 CellsT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerTOR Serine-Threonine KinasesTranscription FactorsConceptsFollicular B helper T cellsAcute viral infectionHelper T cellsTfh cellsT cellsViral infectionT helper 1 cellsHelper T cell subsetsIL-2-mediated activationT cell subsetsDiverse effector functionsT helper 1Dependent cytokine productionTh1 cell fateHelper 1Cell subsetsCytokine productionTh1 cellsInterleukin-2Effector functionsCritical orchestratorsMTOR kinase activityLess proliferationMTORC1 axisReciprocal balanceThe transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa
Marshall HD, Ray JP, Laidlaw BJ, Zhang N, Gawande D, Staron MM, Craft J, Kaech SM. The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa. ELife 2015, 4: e04851. PMID: 25569154, PMCID: PMC4337607, DOI: 10.7554/elife.04851.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationB-LymphocytesCell DifferentiationGene Expression ProfilingGerminal CenterImmunoglobulin Class SwitchingLungMiceMucous MembraneOrthomyxoviridaeOrthomyxoviridae InfectionsSignal TransductionSpecies SpecificityT-Lymphocytes, Helper-InducerTOR Serine-Threonine KinasesTransforming Growth Factor betaConceptsCD4 T cellsFollicular helper cellsTfh cellsAntibody responseT cellsHelper cellsViral infectionCD4 T follicular helper cellsVirus-specific CD4 T cellsIL-2 receptor α chainT Follicular Helper CellsRespiratory viral infectionsAcute viral infectionGrowth factor betaGerminal center reactionReceptor α chainInhibition of mTORIL-2 signalingLung mucosaTfh differentiationHumoral responseRapamycin (mTOR) activationTGF-βRFactor betaCenter reaction
2014
CD4+ 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 abilityTranscription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells
Ray JP, Marshall HD, Laidlaw BJ, Staron MM, Kaech SM, Craft J. Transcription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells. Immunity 2014, 40: 367-377. PMID: 24631156, PMCID: PMC3992517, DOI: 10.1016/j.immuni.2014.02.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralAntibody SpecificityB-LymphocytesCD4 AntigensCD4-Positive T-LymphocytesCell DifferentiationGene Expression ProfilingGene Expression RegulationGerminal CenterImmunoglobulin Class SwitchingInterferon Type ILymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMiceMice, KnockoutSignal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorT-Lymphocytes, Helper-InducerTranscriptomeConceptsTfh cellsType I interferonI interferonViral infectionFollicular helper T cellsT helper 1 cellsAntigen-specific antibody productionGC B cell phenotypeHigh affinity antibody-secreting cellsTfh cell differentiationHelper T cellsB cell memoryLymphocytic choriomeningitis virusB-cell phenotypeAntibody-secreting cellsGerminal center B cellsEffector phenotypeReceptor blockadeAcute infectionFollicular helperIFN-inducible genesT cellsTranscription factor STAT3B cellsAntibody production
2011
Differential Expression of Ly6C and T-bet Distinguish Effector and Memory Th1 CD4+ Cell Properties during Viral Infection
Marshall HD, Chandele A, Jung YW, Meng H, Poholek AC, Parish IA, Rutishauser R, Cui W, Kleinstein SH, Craft J, Kaech SM. Differential Expression of Ly6C and T-bet Distinguish Effector and Memory Th1 CD4+ Cell Properties during Viral Infection. Immunity 2011, 35: 633-646. PMID: 22018471, PMCID: PMC3444169, DOI: 10.1016/j.immuni.2011.08.016.Peer-Reviewed Original ResearchConceptsAcute viral infectionViral infectionEffector cellsTfh cell markersVirus-specific effectorT helper 1Th1 effector cellsT-bet expressionIL-7R expressionMemory precursor cellsTh1 CD4Helper 1Memory TTh1 cellsProliferative responseSecondary infectionEffector typeReliable markerCell markersInfectionPrecursor cellsGene expression profilesLy6CCell featuresCell development