2023
PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2021
The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity
Kuchroo JR, Hafler DA, Sharpe AH, Lucca LE. The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity. Science Immunology 2021, 6: eabf4034. PMID: 34739340, DOI: 10.1126/sciimmunol.abf4034.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsPD-1 blockadeRegulatory T cell functionImmune checkpoint blockadeCheckpoint blockade immunotherapyT cell responsesT cell functionBlockade immunotherapyAdverse eventsAntitumor immunityCheckpoint blockadeCell responsesBlockadeCell functionAutoimmunityMechanistic featuresEdged swordImmunotherapyTumorsCancerImmunityCutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19
Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, Kleinstein SH. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19. The Journal Of Immunology 2021, 206: 2785-2790. PMID: 34049971, PMCID: PMC8627528, DOI: 10.4049/jimmunol.2100135.Peer-Reviewed Original ResearchConceptsSevere COVID-19Mild COVID-19B cell responsesMemory B cellsB cell repertoireB cellsCell repertoireCOVID-19Cell responsesExtrafollicular B cell responsesLong-term immunitySymptomatic COVID-19Onset of symptomsB cell populationsGerminal center reactionProtective immunityPlasma cellsSingle-cell RNA sequencingCenter reactionPatientsCell populationsImmunityRNA sequencingCellsPostvaccinationCirculating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2015
Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins
Willis SN, Stathopoulos P, Chastre A, Compton SD, Hafler DA, O’Connor K. Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins. Frontiers In Immunology 2015, 6: 600. PMID: 26648933, PMCID: PMC4663633, DOI: 10.3389/fimmu.2015.00600.Peer-Reviewed Original ResearchCentral nervous systemB cell responsesMultiple sclerosisB cellsCNS tissueCerebrospinal fluidAntigen specificityNervous systemCell responsesAntigen-driven B cell responsesImmune cell infiltrationMS central nervous systemTertiary lymphoid structuresResident B cellsAntigen-driven responseB cell clonesMS brainsLymphoid structuresCell infiltrationRecombinant human immunoglobulinNeurofilament lightCNS-derived cell linesCandidate antigensAntigen arraysDisease pathology
2014
Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses
Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, Sharpe AH, Quintana FJ, Mathis D, Benoist C, Hafler DA, Kuchroo VK. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity 2014, 40: 569-581. PMID: 24745333, PMCID: PMC4070748, DOI: 10.1016/j.immuni.2014.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedCytokinesEosinophilsFibrinogenForkhead Transcription FactorsGene Expression ProfilingGene Expression RegulationImmunosuppression TherapyLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, ImmunologicRespiratory HypersensitivityTh1-Th2 BalanceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsTreg cell subsetsTh2 cell responsesTreg cellsCell subsetsCell responsesProinflammatory T helper 1T effector cell proliferationTreg cell-mediated suppressionFibrinogen-like protein 2Allergic airway inflammationT regulatory (Treg) cellsTh2 cytokine productionSuppression of Th1T helper 1Effector cell proliferationTreg signature genesProinflammatory Th1TIGIT expressionAirway inflammationTh17 cellsRegulatory cellsHelper 1Cytokine productionT cellsImmune response
2010
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)
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
2008
TIMs: central regulators of immune responses
Hafler DA, Kuchroo V. TIMs: central regulators of immune responses. Journal Of Experimental Medicine 2008, 205: 2699-2701. PMID: 19015312, PMCID: PMC2585854, DOI: 10.1084/jem.20082429.Peer-Reviewed Original ResearchConceptsExhausted T cellsT cell exhaustionHIV infectionPD-1T cellsCell exhaustionMucin domain-containing protein 3Chronic HIV infectionChronic viral infectionsHuman HIV infectionT cell responsesChronic viral diseasesT-cell immunoglobulinDomain-containing protein 3Novel therapeutic targetTim-3Opportunistic infectionsCell immunoglobulinImmune responseTherapeutic targetViral infectionCell responsesProtein 3InfectionViral diseases
2007
Multispecific responses by T cells expanded by endogenous self‐peptide/MHC complexes
Cai G, Hafler DA. Multispecific responses by T cells expanded by endogenous self‐peptide/MHC complexes. European Journal Of Immunology 2007, 37: 602-612. PMID: 17304631, DOI: 10.1002/eji.200636787.Peer-Reviewed Original ResearchConceptsT cellsHuman T cell responsesSelf-peptide/MHCSelf-peptide/MHC complexesEndogenous self-antigenPercentage of CD4Pathological immune responsesT cell responsesAntigen-presenting cellsT cell clonesCell cycleMultispecific responseMHC determinantsSelf antigensAntigen stimulationHealthy subjectsImmune responseAntigen reactivityCD4Cell responsesMultiple antigensCD28 costimulationMHC complexesCell clonesTCRbeta chain
2005
High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model
Ellmerich S, Mycko M, Takacs K, Waldner H, Wahid FN, Boyton RJ, King RH, Smith PA, Amor S, Herlihy AH, Hewitt RE, Jutton M, Price DA, Hafler DA, Kuchroo VK, Altmann DM. High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model. The Journal Of Immunology 2005, 174: 1938-1946. PMID: 15699121, DOI: 10.4049/jimmunol.174.4.1938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationCell MovementCentral Nervous SystemDisease Models, AnimalDisease ProgressionDNA-Binding ProteinsEpitopes, T-LymphocyteHLA-DR AntigensHLA-DR Serological SubtypesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMultiple SclerosisMyelin Basic ProteinParalysisPeptide FragmentsReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell responsesHLA-DR15Multiple sclerosisDeterminant spreadSpontaneous diseaseCell responsesCD4 T cell recognitionCNS tissue damageHuman multiple sclerosisMultiple sclerosis modelT cell reactivityExperimental allergic encephalomyelitisMyelin oligodendrocyte glycoproteinT cell recognitionMyelin basic proteinAllergic encephalomyelitisMyelin epitopesPeptide immunotherapyAxonal degenerationCell reactivityOligodendrocyte glycoproteinPathogenic roleT cellsHigh incidenceTransgenic mice
2004
An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells
Vijayakrishnan L, Slavik JM, Illés Z, Greenwald RJ, Rainbow D, Greve B, Peterson LB, Hafler DA, Freeman GJ, Sharpe AH, Wicker LS, Kuchroo VK. An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells. Immunity 2004, 20: 563-575. PMID: 15142525, DOI: 10.1016/s1074-7613(04)00110-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntigens, CDAntigens, DifferentiationAutoimmune DiseasesB7-1 AntigenBlotting, WesternCloning, MolecularCTLA-4 AntigenFemaleFlow CytometryHumansMembrane ProteinsMiceMice, Inbred NODMolecular Sequence DataReceptors, Antigen, T-CellReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionT-LymphocytesConceptsCytotoxic T-lymphocyte-associated antigen 4T cell responsesT cellsNOD miceAutoimmune diseasesT cell-mediated autoimmune diseaseT-lymphocyte-associated antigen 4Cell responsesCell-mediated autoimmune diseaseSusceptible NOD miceRegulatory T cellsNOD congenic miceCTLA-4 locusAntigen-4B7-1B7-2Primary T cellsCongenic miceSplice variantsMiceNegative signalingMYPPPY motifDiseaseType IGenetic linkage
2003
Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function
Lim DG, Slavik JM, Bourcier K, Smith KJ, Hafler DA. Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function. Journal Of Experimental Medicine 2003, 198: 99-109. PMID: 12847139, PMCID: PMC2196091, DOI: 10.1084/jem.20021796.Peer-Reviewed Original ResearchConceptsT cell functionT cell clonesCell functionReactive T cell clonesCell clonesT cell responsesDifferent T cell responsesIndividual T cell clonesHLA-A2 moleculesAltered peptide ligandHLA-A2 peptideRecognition of MHCT cell receptorMHC-peptide complexesPolymorphic amino acidsFunctional outcomeHLA-A2Peptide ligandsAgonist functionMHC moleculesCell responsesEarly intracellularLong-term expressionCell receptorAntigen recognition
2002
Strength of prior stimuli determines the magnitude of secondary responsiveness in CD8+ T cells
Lim DG, Höllsberg P, Hafler DA. Strength of prior stimuli determines the magnitude of secondary responsiveness in CD8+ T cells. Cellular Immunology 2002, 217: 36-46. PMID: 12425999, DOI: 10.1016/s0008-8749(02)00511-7.Peer-Reviewed Original ResearchConceptsT cellsSecondary responsivenessCostimulatory moleculesInduction of CD8Magnitude of CD8T cell responsesT cell anergyCell anergyCD8Prior stimulusSecondary stimulationPrimary stimulationCell responsesCellular mechanismsFollowing activationPeptide ligandsActivation thresholdStimulationCellsResponsivenessHigh levelsCD4AnergyStimuliStrength of signal
2001
Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes
Slavik J, Lim D, Burakoff S, Hafler D. Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes. The Journal Of Immunology 2001, 166: 3201-3209. PMID: 11207273, DOI: 10.4049/jimmunol.166.5.3201.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCD2 AntigensCD28 AntigensCD3 ComplexCD8 AntigensCD8-Positive T-LymphocytesCell Line, TransformedClone CellsDose-Response Relationship, DrugDose-Response Relationship, ImmunologicDrug ResistanceEnzyme ActivationEpitopes, T-LymphocyteHLA-A AntigensHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationMajor Histocompatibility ComplexModels, ImmunologicalRibosomal Protein S6 KinasesSirolimusT-Lymphocyte SubsetsConceptsT cell clonesT cellsEffect of rapamycinHuman T cell responsesPeripheral blood T cellsCell clonesHeterogeneous proliferative responsesT cell responsesBlood T cellsT cell proliferationSpecific costimulatory signalsGraft infiltrationResistant proliferationInhibition of AgGraft rejectionHuman CD8IL-2RT lymphocytesProliferative responseCostimulatory signalsCell responsesPresence of rapamycinCell proliferationRapamycinProliferation
1999
Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone.
Milner J, Kent S, Ashley T, Wilson S, Strominger J, Hafler D. Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone. The Journal Of Immunology 1999, 163: 2522-9. PMID: 10452989, DOI: 10.4049/jimmunol.163.5.2522.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAntibodies, BlockingAntibodies, MonoclonalAntigens, CD1Antigens, CD1dAntigens, Differentiation, B-LymphocyteApoptosisAutocrine CommunicationCD3 ComplexCD4-Positive T-LymphocytesClone CellsDexamethasoneDose-Response Relationship, ImmunologicFas ReceptorHistocompatibility Antigens Class IIHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationReceptors, Antigen, T-Cell, alpha-betaSignal TransductionT-Lymphocyte SubsetsConceptsActivation-induced cell deathT cell clonesT cellsTCR signal strengthCell clonesAutocrine IL-2 productionNK T cellsT cell responsesT cell subsetsInhibition of CD4Anti-CD3 stimulationT cell proliferationEffect of dexamethasoneMHC class IIIL-2 productionPresence of dexamethasoneExogenous corticosteroidsCell subsetsImmunomodulatory consequencesDexamethasone treatmentImmune responseCD4High dosesLow dosesCell responses
1998
T helper cell differentiation in multiple sclerosis and autoimmunity
Martin R, Ruddle N, Reingold S, Hafler D. T helper cell differentiation in multiple sclerosis and autoimmunity. Trends In Immunology 1998, 19: 495-498. PMID: 9818541, DOI: 10.1016/s0167-5699(98)01345-0.Peer-Reviewed Original Research
1996
IL-12 induces human T cells secreting IL-10 with IFN-gamma.
Windhagen A, Anderson DE, Carrizosa A, Williams RE, Hafler DA. IL-12 induces human T cells secreting IL-10 with IFN-gamma. The Journal Of Immunology 1996, 157: 1127-31. PMID: 8757617, DOI: 10.4049/jimmunol.157.3.1127.Peer-Reviewed Original ResearchConceptsIL-10T cell responsesIL-12T cell clonesIFN-gammaT cellsT cell linesHuman T cellsMyelin basic protein-reactive T cell clonesCell responsesPredominant T cell responseShort-term T cell linesConcomitant secretionHuman T cell responsesCell clonesAg-specific stimulationIFN-gamma secretionIFN-gamma productionAnti-CD3 mAbCell linesMyelin basic proteinGamma AbIL-2IL-4Cytokine secretion
1995
T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans.
Markovic-Plese S, Fukaura H, Zhang J, al-Sabbagh A, Southwood S, Sette A, Kuchroo VK, Hafler DA. T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans. The Journal Of Immunology 1995, 155: 982-92. PMID: 7541828, DOI: 10.4049/jimmunol.155.2.982.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsPLP epitopesMHC class II isotypesPLP-reactive T cellsShort-term T cell linesCryptic epitopesProteolipid proteinT cell responsesT cell recognitionClass II isotypesT cell linesIndividual synthetic peptidesControl subjectsMHC restrictionImmune responseDR2 moleculesProliferative responseImmunodominant epitopesPLP peptidesProtein AgCell responsesCentral nervous system myelin proteinsMyelin proteinsEpitopes
1994
Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide.
Wucherpfennig KW, Zhang J, Witek C, Matsui M, Modabber Y, Ota K, Hafler DA. Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. The Journal Of Immunology 1994, 152: 5581-92. PMID: 7514641, DOI: 10.4049/jimmunol.152.11.5581.Peer-Reviewed Original ResearchConceptsT cellsNormal subjectsImmunodominant myelin basic protein peptideMBP-specific T cell linesDR2 haplotypeSpecific T cell clonesTCR beta-chain sequencesReactive T cellsT cell responsesHLA-DR moleculesT cell clonesIdentical TCR sequencesMyelin basic protein peptideIL-2 stimulationT cell linesHuman T cellsAlpha-chain rearrangementMyelin basic proteinMultiple sclerosisBeta chain sequencesTCR rearrangementsPatientsCell responsesTCR alphaTCR sequences
1993
MHC-Restricted Depletion of Human Myelin Basic Protein-Reactive T Cells by T Cell Vaccination
Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-Restricted Depletion of Human Myelin Basic Protein-Reactive T Cells by T Cell Vaccination. Science 1993, 261: 1451-1454. PMID: 7690157, DOI: 10.1126/science.7690157.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsT cell vaccinationT cellsT cell linesCell vaccinationMyelin basic protein-reactive T cellsRegulatory T cell linesMBP-reactive T cellsExperimental autoimmune diseasesReactive T cellsT cell responsesMajor histocompatibility antigensCell linesMyelin basic proteinMultiple sclerosisAutoimmune diseasesHistocompatibility antigensCell responsesVaccinationBasic proteinRecipientsPresent studyCellsCD8Sclerosis