2025
Tissue‐Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells
Chen S, Craft J. Tissue‐Resident T Cells That Promote Humoral Immunity: Emerging From the Shadow of T Follicular Helper Cells. Immunological Reviews 2025, 334: e70056. PMID: 40890948, PMCID: PMC12402542, DOI: 10.1111/imr.70056.Peer-Reviewed Original ResearchConceptsB cell folliclesB cell maturationHelper cellsT cellsB cellsB-cell follicles of secondary lymphoid organsFollicles of secondary lymphoid organsT follicular helper (Tfh) cellsHumoral immunityRegulate B-cell maturationTissue-resident T cellsT Follicular Helper CellsFunction of T cellsAntibody-producing plasma cellsB cell helpDevelopment of humoral immunitySecondary lymphoid organsLocal humoral responseNon-lymphoid tissuesHumoral immune responseImmune challengeSystemic immune protectionCentral nervous systemTfh cellsImmunoglobulin class switch recombination
2024
Angioimmunoblastic T-cell lymphoma: Current Diagnostic Insights and Advances
Matsumoto N, Xu M. Angioimmunoblastic T-cell lymphoma: Current Diagnostic Insights and Advances. Human Pathology 2024, 156: 105696. PMID: 39571692, DOI: 10.1016/j.humpath.2024.105696.Peer-Reviewed Original ResearchConceptsAngioimmunoblastic T-cell lymphomaT-cell lymphomaT Follicular Helper CellsDevelopment of novel treatment strategiesEpigenetic regulatory genesNovel treatment strategiesAngioimmunoblastic typeCell lymphomaClinical presentationHelper cellsDiagnostic challengeT cellsHistopathological featuresInflammatory milieuTreatment optionsClonal expansionDriver mutationsTreatment strategiesAggressive typeLymphomaMultistep processMutationsRegulatory genesPrognosisTET2T Follicular Helper Cell Heterogeneity
Song W, Craft J. T Follicular Helper Cell Heterogeneity. Annual Review Of Immunology 2024, 42: 127-152. PMID: 38060987, DOI: 10.1146/annurev-immunol-090222-102834.Peer-Reviewed Original ResearchTfh cellsHumoral immune memoryTfh cell subsetsFollicular helper cellsGerminal center responseCell subsetsHelper cellsHumoral immunityImmune memoryCenter responseCell responsesImmunoglobulin affinity maturationAffinity maturationCritical contributorCellsPublication dateClass switch recombinationImmunoglobulin class switch recombinationCell heterogeneityTlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl miceDOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells.
Williams A, Siniscalco E, Grassmann J, Craft J, Eisenbarth S, Uthaman G. DOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells. The Journal Of Immunology 2024, 212: 0620_4120-0620_4120. DOI: 10.4049/jimmunol.212.supp.0620.4120.Peer-Reviewed Original ResearchPeanut-specific IgET cellsSpecific IgEFood allergyT Follicular Helper CellsCD4+ T cellsDOCK8-deficient patientsFood-specific IgEPeanut-specific IgE.Human T cellsCells in vitroDifferentiation in vivoSevere food allergyTfh cellsRegulatory populationsOvercome toleranceHelper cellsDeficient patientsSpecific IgE.DOCK8IgE productionSTAT3 mutationsMiceCholera toxinIgE
2023
Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells
Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q, Lopez R, Adelekan-Kamara Y, Fan M, Pober J, Tellides G, Jane-wit D. Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells. Frontiers In Immunology 2023, 14: 1248027. PMID: 37915586, PMCID: PMC10616247, DOI: 10.3389/fimmu.2023.1248027.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryHuman skin xenograftsSkin xenograftsT cellsPolyfunctional cytokine responsesSolid organ transplantationT cell subsetsResponse of CD4Expression of ICOST cell populationsHumanized mouse modelPeripheral helper cellsAllograft lossIL-21PD-1Reperfusion injuryCytokine responsesVascular inflammationPolyclonal expansionHelper cellsOrgan transplantationMouse modelClinical problemCostimulatory signalsDistinct subsetsT follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui C, Craft J, Joshi N. T follicular helper cells in cancer, tertiary lymphoid structures, and beyond. Seminars In Immunology 2023, 69: 101797. PMID: 37343412, DOI: 10.1016/j.smim.2023.101797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor-associated tertiary lymphoid structuresFollicular helper cellsCD8 T cellsTertiary lymphoid structuresSecondary lymphoid organsT cellsHelper cellsLymphoid structuresImmune cellsB cellsCD4 T follicular helper cellsT Follicular Helper CellsTumor-infiltrating immune cellsCurrent immunotherapy regimensCheckpoint blockade immunotherapyCD4 T cellsImmune cell componentsLimited response rateFunctional immune cellsNovel therapeutic targetPotential therapeutic benefitT cell-B cell interactionsBlockade immunotherapyImmunotherapy regimensLymphoid organs
2022
Gut Microbiota and Immune Modulatory Properties of Human Breast Milk Streptococcus salivarius and S. parasanguinis Strains
Li S, Li N, Wang C, Zhao Y, Cao J, Li X, Zhang Z, Li Y, Yang X, Wang X, Che C, Zhao Y, Wang L, Zhao L, Shen J. Gut Microbiota and Immune Modulatory Properties of Human Breast Milk Streptococcus salivarius and S. parasanguinis Strains. Frontiers In Nutrition 2022, 9: 798403. PMID: 35273986, PMCID: PMC8901577, DOI: 10.3389/fnut.2022.798403.Peer-Reviewed Original ResearchImmune-modulatory propertiesHuman breast milkGut microbiotaBreast milkModulatory propertiesAnti-inflammatory Treg cellsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsIleal mRNA expressionBlood mononuclear cellsT helper cellsAnti-inflammatory potentialPostnatal week 3Postnatal day 1Microbiota α-diversityImmune response genesTreg cellsBreast feedingHelper cellsMononuclear cellsIleal expressionSuckling miceGut immunityWeaning miceInfant gutHigh-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
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4Expression of Foxp3 by T follicular helper cells in end-stage germinal centers
Jacobsen J, Hu W, R Castro T, Solem S, Galante A, Lin Z, Allon S, Mesin L, Bilate A, Schiepers A, Shalek A, Rudensky A, Victora G. Expression of Foxp3 by T follicular helper cells in end-stage germinal centers. Science 2021, 373 PMID: 34437125, PMCID: PMC9007630, DOI: 10.1126/science.abe5146.Peer-Reviewed Original ResearchConceptsFollicular helper cellsGerminal centersHelper cellsFormation of GCsExpression of Foxp3Effective antibody responseTranscription factor Foxp3Acute surgeAntibody responseFactor Foxp3T cellsFoxp3Immunoglobulin somatic hypermutationGC sizeAffinity maturationPotential regulatorCellsEctopic expressionSomatic hypermutationExpressionAntibodiesCD4+ T cells that help B cells – a proposal for uniform nomenclature
Eisenbarth SC, Baumjohann D, Craft J, Fazilleau N, Ma CS, Tangye SG, Vinuesa CG, Linterman MA. CD4+ T cells that help B cells – a proposal for uniform nomenclature. Trends In Immunology 2021, 42: 658-669. PMID: 34244056, PMCID: PMC8324560, DOI: 10.1016/j.it.2021.06.003.Peer-Reviewed Original ResearchConceptsTfh-like cellsB cellsT cellsFollicular helper cellsAntigen-primed B cellsSecondary lymphoid tissuesTranscription factor Bcl6B cell differentiationHelper cellsHumoral immunityLymphoid tissueChemokine receptorsAnatomical sitesImmune challengeDistinct subsetsDifferent isotypesCD4TfhCellular plasticityCellsCell differentiationUniform nomenclatureCytokinesImmunityAntibodiesT 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 challengeDendritic Cell Regulation of T Helper Cells
Yin X, Chen S, Eisenbarth SC. Dendritic Cell Regulation of T Helper Cells. Annual Review Of Immunology 2021, 39: 1-32. PMID: 33710920, DOI: 10.1146/annurev-immunol-101819-025146.Peer-Reviewed Original ResearchConceptsDendritic cellsProfessional antigen-presenting cellsDendritic Cell RegulationDifferent DC subsetsT helper cellsAntigen-presenting cellsAdaptive immune responsesT lymphocyte differentiationTh cell differentiationDC subsetsRegulatory cellsDistinct CD4Follicular helperImmune toleranceSubset phenotypesImmune activationHelper cellsImmune cellsImmune responseImmune systemHeterogeneous subsetLymphocyte differentiationLocal tissue microenvironmentTissue microenvironmentCells
2020
Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization
Zhang B, Liu E, Gertie JA, Joseph J, Xu L, Pinker EY, Waizman DA, Catanzaro J, Hamza KH, Lahl K, Gowthaman U, Eisenbarth SC. Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization. Science Immunology 2020, 5 PMID: 32385053, PMCID: PMC8518330, DOI: 10.1126/sciimmunol.aay2754.Peer-Reviewed Original ResearchConceptsFood antigensIgE productionIgA productionFollicular helper cellsMinority of miceHelper cell requirementDominant antibody isotypeCross-reactive IgAFollicular regulatoryDietary antigensAllergic sensitizationTolerogenic responsesMucosal adjuvantMucosal IgAHelper cellsAntibody isotypesStool samplesImmunoglobulin AT cellsFood exposureGerminal centersFood allergensAntibody productionIgADietary exposureHSV-2 infects T follicular helper cells to promote HIV reactivation
Pierce C, Loh L, Preston-Hurlburt P, Herold K, Herold B. HSV-2 infects T follicular helper cells to promote HIV reactivation. The Journal Of Immunology 2020, 204: 247.24-247.24. DOI: 10.4049/jimmunol.204.supp.247.24.Peer-Reviewed Original ResearchCD4 T cellsFollicular helper cellsHIV reactivationHSV-2T cellsTfh cellsIL-32Helper cellsSystemic effectsCD4 T-cell subpopulationsT Follicular Helper CellsHSV-2 recurrencesHSV-2 seropositiveT cell subpopulationsGlobal HIV epidemicPotential systemic effectsT cell linesSeronegative womenIL-32γHigh HIVViral loadHIV transmissionLatent HIVProinflammatory cytokinesHIV epidemicMutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response
Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM. Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Cancer Cell 2020, 37: 655-673.e11. PMID: 32396861, PMCID: PMC7298875, DOI: 10.1016/j.ccell.2020.04.004.Peer-Reviewed Original ResearchConceptsFollicular lymphomaB cellsIndolent tumorsCell helpFollicular dendritic cell networksB cell requirementDendritic cell networksFollicular helper cellsGerminal center B cellsGC B cellsHelper cellsImmunological nicheImmune responseMalignant transformationHuman follicular lymphomaEZH2 mutationsPrevents inductionFunction mutationsTumorsCell requirementsCellsMutant EZH2LymphomaMutations
2019
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Liu L, Fang C, Fu W, Jiang B, Li G, Qin L, Rosenbluth J, Gong G, Xie CB, Yoo P, Tellides G, Pober JS, Jane-Wit D. Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production. Circulation 2019, 141: 464-478. PMID: 31744330, PMCID: PMC7035199, DOI: 10.1161/circulationaha.119.042501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDelayed Graft FunctionFemaleGene Expression RegulationHuman Umbilical Vein Endothelial CellsHumansImmunoglobulin MInflammasomesInterleukin-18Interleukin-18 Receptor alpha SubunitIsoantibodiesMiceMice, SCIDOrgan TransplantationReperfusion InjurySignal TransductionT-Lymphocytes, Helper-InducerConceptsIschemia-reperfusion injuryDonor-specific antibodiesPeripheral helper cellsIL-18Helper cellsReperfusion injuryInterleukin-18IL-18R1Donor-specific antibody formationEndothelial cellsDelayed graft functionLate allograft lossT cell populationsAlloantibody productionAllograft lossChronic rejectionGraft functionClinical manifestationsPD-L2Antibody formationHumanized modelAllograft tissueImmunoglobulin MPatient specimensComplement activationAdaptive Immunity: Effector Functions, Regulation, and Vaccination
Kavathas P, Krause P, Ruddle N. Adaptive Immunity: Effector Functions, Regulation, and Vaccination. 2019, 75-95. DOI: 10.1007/978-3-030-25553-4_5.ChaptersAntigen-presenting cellsT cellsB cellsImmune responseInnate cellsEffector cellsInnate antigen-presenting cellsCD4 T helper cellsEffector T cellsB memory cellsT helper cellsSecondary lymphoid organsNaive T cellsBalanced immune responsePathogen-infected host cellsCD4 subsetCytokine milieuHelper cellsLymphoid organsEffector TPlasma cellsEffector functionsAdaptive immuneTypes of pathogensMacrophage response
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