2023
ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samplesBSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structures
2018
Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo
Dominguez-Villar M, Raddassi K, Danielsen AC, Guarnaccia J, Hafler DA. Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo. Journal Of Autoimmunity 2018, 96: 40-49. PMID: 30122421, PMCID: PMC7882197, DOI: 10.1016/j.jaut.2018.08.002.Peer-Reviewed Original ResearchConceptsT cellsMultiple sclerosisT cell effector phenotypeRelapsing-remitting multiple sclerosisRegulatory T cell populationTh1-like phenotypeRegulatory T cellsPro-inflammatory cytokinesT-cell phenotypeT cell populationsExpression of Th1Immune cell functionRegulatory T cell plasticityT cell plasticityCentral nervous systemExpression of markersCell migratory capacityImportant immunomodulatory functionsExcessive Th1Fingolimod treatmentExhaustion markersTh17 cytokinesEffector phenotypeLymph nodesSerum levels
2011
CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis
Baecher-Allan CM, Costantino CM, Cvetanovich GL, Ashley CW, Beriou G, Dominguez-Villar M, Hafler DA. CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis. The Journal Of Immunology 2011, 186: 3317-3326. PMID: 21300823, PMCID: PMC4467560, DOI: 10.4049/jimmunol.1002502.Peer-Reviewed Original ResearchMeSH KeywordsAdultCD2 AntigensCD4 AntigensCell DifferentiationCells, CulturedCoculture TechniquesFetal BloodForkhead Transcription FactorsHumansInfant, NewbornInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLymphocyte ActivationMiddle AgedMultiple SclerosisSignal TransductionT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryYoung AdultConceptsMultiple sclerosisIL-17Suppressive capacityDR cellsRegulatory T cell populationEffector T cellsExpression of CD127T cell populationsMechanism of actionTreg populationRegulatory cellsIL-10Effector cellsHLA-DREffector subsetsHuman TregsCD2 costimulationMemory TregsT cellsTregsAdult bloodLow expressionSclerosisPatientsCD127
2006
Human regulatory T cells and their role in autoimmune disease
Baecher‐Allan C, Hafler DA. Human regulatory T cells and their role in autoimmune disease. Immunological Reviews 2006, 212: 203-216. PMID: 16903916, DOI: 10.1111/j.0105-2896.2006.00417.x.Peer-Reviewed Original ResearchConceptsRegulatory T cellsAutoimmune diseasesSelf-reactive cellsT cellsHealthy individualsHuman natural regulatory T cellsSelf-reactive T cellsNatural regulatory T cellsHuman regulatory T cellsPathologic T cellsReduced inhibitory functionSpecific autoimmune diseasesT cell populationsMature T cellsT cell maturationNon-responsive stateRegulatory cellsNatural CD4Peripheral circulationImmune systemPatientsDiseaseInhibitory functionNumber of mechanismsCellsMHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells
Baecher-Allan C, Wolf E, Hafler DA. MHC Class II Expression Identifies Functionally Distinct Human Regulatory T Cells. The Journal Of Immunology 2006, 176: 4622-4631. PMID: 16585553, DOI: 10.4049/jimmunol.176.8.4622.Peer-Reviewed Original ResearchConceptsContact-dependent suppressionRegulatory T cellsT cellsCD4 cellsDR expressionFunctional MHC class II moleculesRegulatory T cell populationHuman regulatory T cellsMHC class II determinantsIL-10 secretionClass II determinantsMHC class II moleculesHigh Foxp3 expressionMHC-II expressionEarly IL-4T cell populationsT cell nonresponsivenessClass II moleculesEx vivo expressionVivo expressionHuman CD4 cellsSubpopulations CD4Treg populationFoxp3 expressionIL-4
2003
Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*
Slavik JM, Lim DG, Burakoff SJ, Hafler DA. Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*. Journal Of Biological Chemistry 2003, 279: 910-919. PMID: 14573608, DOI: 10.1074/jbc.m209733200.Peer-Reviewed Original ResearchMeSH KeywordsAnnexin A5Antibiotics, AntineoplasticBcl-X ProteinCD28 AntigensCD3 ComplexCD8-Positive T-LymphocytesCell Cycle ProteinsCell DivisionColoring AgentsCyclin DCyclin-Dependent Kinase Inhibitor p27CyclinsDose-Response Relationship, DrugDown-RegulationEnzyme InhibitorsEstersFluoresceinsHumansKineticsLymphocytesPhosphatidylinositol 3-KinasesProtein BindingProto-Oncogene Proteins c-bcl-2Signal TransductionSirolimusTime FactorsT-LymphocytesTumor Suppressor ProteinsConceptsInhibitor of phosphoinositideT cell receptorMammalian cell typesCell receptorBcl-xL inductionAction of rapamycinBcl-xL expressionT cellsHuman cellsCell survivalP27 Kip1Resistant proliferationCell typesPhosphoinositideHuman CD8RapamycinCellular proliferationEffect of rapamycinMicrobial infectionsCell populationsHigh-affinity T-cell receptorsSelective immunosuppressive effectT Cells CorrelateT cell populationsProliferationIn vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis
Schmied M, Duda PW, Krieger JI, Trollmo C, Hafler DA. In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis. Clinical Immunology 2003, 106: 163-174. PMID: 12706402, DOI: 10.1016/s1521-6616(03)00020-2.Peer-Reviewed Original ResearchConceptsGA-reactive T cellsT cell reactivityT cellsRR-MSMultiple sclerosisCell reactivityT cell peripheral toleranceTh2-type T cellsT cell frequenciesMonths of treatmentT cell hyporesponsivenessT cell populationsT cell nonresponsivenessT cell anergyHyporesponsive T cellsMechanism of actionMyelin antigensGlatiramer acetatePeripheral toleranceCell hyporesponsivenessPeripheral bloodClonal eliminationIL-2Cell anergySubcutaneous administration
2000
Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate
Duda P, Krieger J, Schmied M, Balentine C, Hafler D. Human and Murine CD4 T Cell Reactivity to a Complex Antigen: Recognition of the Synthetic Random Polypeptide Glatiramer Acetate. The Journal Of Immunology 2000, 165: 7300-7307. PMID: 11120865, DOI: 10.4049/jimmunol.165.12.7300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCD4-Positive T-LymphocytesCell Line, TransformedCell SeparationClone CellsDose-Response Relationship, ImmunologicFemaleGlatiramer AcetateHematopoietic Stem CellsHLA-DR AntigensHumansImmunizationImmunologic MemoryImmunomagnetic SeparationInfant, NewbornLeukocytes, MononuclearLymphocyte ActivationLymphocyte CountMiceMice, Inbred BALB CMice, Inbred C57BLMultiple Sclerosis, Relapsing-RemittingPeptidesSpleenTh1 CellsTh2 CellsConceptsT cell populationsHLA class II DRGlatiramer acetateT cell proliferationClass II DRII DRT cellsCD4 T cell reactivityGA-reactive T cellsHuman T cell proliferative responsesT cell precursor frequencyCell populationsSpecific human T cell clonesT cell proliferative responsesHuman T cell clonesMemory T cellsT cell reactivityMultiple sclerosis patientsRecent clinical findingsCell precursor frequencyCell proliferative responsesCell proliferationT cell clonesDose-dependent proliferationHealthy human adultsA novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis
Kipp B, Bar‐Or A, Gausling R, Oliveira E, Fruhan S, Stuart W, Hafler D. A novel population of B7‐1+ T cells producing intracellular IL‐4 is decreased in patients with multiple sclerosis. European Journal Of Immunology 2000, 30: 2092-2100. PMID: 10940899, DOI: 10.1002/1521-4141(200007)30:7<2092::aid-immu2092>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsT cell receptorIntracellular IL-4Multiple sclerosisT cellsB7-1IL-4Autoimmune diseasesTNF-alphaIFN-gammaIL-4-producing T cellsLittle IL-4Immunoregulatory T cellsIL-4 productionIntracellular IFN-gammaT cell populationsLittle IFN-gammaNovel populationDiverse TCR repertoireMHC class IIHuman T cellsShort-term cultureCell surface moleculesTCR repertoireNormal subjectsPatientsParadoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population
Anderson D, Bieganowska K, Bar-Or A, Oliveira E, Carreno B, Collins M, Hafler D. Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population. Nature Medicine 2000, 6: 211-214. PMID: 10655112, DOI: 10.1038/72323.Peer-Reviewed Original ResearchConceptsCTLA-4 blockadeT cell populationsCTLA-4T cellsMonoclonal antibodiesB7-1B7-2Immune responseCytotoxic T-lymphocyte antigen-4Whole T cell populationsT-lymphocyte antigen-4Antigen-specific T cellsT cell activation stateHuman T cell populationsT cell functionT cell receptor signalsCo-stimulatory signalsDifferent T cellsT cell stimulationEffect of B7T cell activationActivation stateT cell receptorHuman T cellsFab fragments
1998
Identification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection.
Pohl-Koppe A, Balashov K, Steere A, Logigian E, Hafler D. Identification of a T cell subset capable of both IFN-gamma and IL-10 secretion in patients with chronic Borrelia burgdorferi infection. The Journal Of Immunology 1998, 160: 1804-10. PMID: 9469440, DOI: 10.4049/jimmunol.160.4.1804.Peer-Reviewed Original ResearchConceptsT cell linesIFN-gamma/ILB. burgdorferi infectionIFN-gammaBurgdorferi infectionT cellsIL-12Lyme patientsCell linesLyme diseaseVigorous humoral immune responseIL-10 secretionExogenous IL-12T cell subsetsT cell populationsHumoral immune responseNovel populationB. burgdorferiBorrelia burgdorferi infectionPrecursor T cellsWhole mononuclear cellsHuman T cellsGroups of subjectsIL-10Cell subsets
1996
Antigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis
FUKAURA H, KENT S, PIETRUSEWICZ M, KHOURY S, WEINER H, HAFLER D. Antigen‐specific TGF‐β1 Secretion with Bovine Myelin Oral Tolerization in Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1996, 778: 251-257. PMID: 8610978, DOI: 10.1111/j.1749-6632.1996.tb21133.x.Peer-Reviewed Original ResearchConceptsRelapsing-remitting MS patientsHuman autoimmune diseasesOral tolerizationMultiple sclerosisAutoimmune diseasesT cell linesMS patientsCytokine secretionT cellsAutoreactive T-cell populationsAutoreactive T cellsT cell populationsT-cell fractionCNS white matterFed patientsIL-4Inflammatory responseΒ1 secretionIFN-gammaTolerizationWhite matterPatientsSclerosisBovine myelinSecretion
1993
Increased Protein Kinase C Activity in Human Memory T Cells
Höllsberg P, Melinek J, Benjamin D, Hafler D. Increased Protein Kinase C Activity in Human Memory T Cells. Cellular Immunology 1993, 149: 170-179. PMID: 8099849, DOI: 10.1006/cimm.1993.1145.Peer-Reviewed Original ResearchConceptsCD26 T cellsMemory T cellsT cell populationsMemory T cell populationsT cellsT cell receptorProliferative responseCell populationsPeripheral blood T cellsHuman memory T cellsMemory T cell functionCD26 antigen expressionT-cell surface antigensPKC activityBlood T cellsT cell functionTCR/CD3 pathwayDifferentiated T cellsCell surface antigensCD26 mAbCD26- subsetAntigen challengeAntigen expressionCD26 antigenCD26 expressionHuman fetal liver gamma/delta T cells predominantly use unusual rearrangements of the T cell receptor delta and gamma loci expressed on both CD4+CD8- and CD4-CD8- gamma/delta T cells.
Wucherpfennig KW, Liao YJ, Prendergast M, Prendergast J, Hafler DA, Strominger JL. Human fetal liver gamma/delta T cells predominantly use unusual rearrangements of the T cell receptor delta and gamma loci expressed on both CD4+CD8- and CD4-CD8- gamma/delta T cells. Journal Of Experimental Medicine 1993, 177: 425-432. PMID: 8093893, PMCID: PMC2190895, DOI: 10.1084/jem.177.2.425.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCD4-Positive T-LymphocytesClone CellsGene Rearrangement, delta-Chain T-Cell Antigen ReceptorGene Rearrangement, gamma-Chain T-Cell Antigen ReceptorHumansLiverMolecular Sequence DataOligodeoxyribonucleotidesReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocyte SubsetsConceptsGamma/delta T cellsGamma/delta T cell clonesDelta T cellsT cell clonesGamma/delta T cell populationsT cell populationsT cellsFetal liverT cell developmentCell clonesCD4-CD8TCR delta chain transcriptsUnusual T-cell populationCell populationsFetal immune systemDelta-chain transcriptsGene rearrangementsT-cell receptor gammaGamma chain rearrangementT-cell receptor deltaHuman fetal liverTCR delta chainCell developmentAlpha/betaFetal thymus
1992
Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions.
Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA. Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 4588-4592. PMID: 1374907, PMCID: PMC49128, DOI: 10.1073/pnas.89.10.4588.Peer-Reviewed Original ResearchConceptsGamma delta T cellsDelta T cellsT cellsMultiple sclerosisMS plaquesCentral nervous system inflammatory processesAcute multiple sclerosis lesionsT cell receptor repertoireGamma delta T-cell receptor repertoireHeat shock proteinsAcute MS plaquesMS plaque tissueNormal CNS tissueDistinct lymphocyte populationsT cell populationsMultiple sclerosis lesionsShock proteinsAcute plaquesReactive astrocytesLymphocyte populationsInflammatory processFoamy macrophagesCNS tissueInflammatory sitesQuantitative immunohistochemistry
1991
The coexpression of CD45RA and CD45RO isoforms on T cells during the S/G2/M stages of cell cycle
LaSalle J, Hafler D. The coexpression of CD45RA and CD45RO isoforms on T cells during the S/G2/M stages of cell cycle. Cellular Immunology 1991, 138: 197-206. PMID: 1833074, DOI: 10.1016/0008-8749(91)90144-z.Peer-Reviewed Original ResearchConceptsT cell clonesCell cycleT cellsCD45RA expressionCord bloodTyrosine phosphatase CD45Cell clonesM stageCell cycle stagePHA activationPeripheral blood T cellsCD45RO T cellsCoexpression of CD45RAG2/M stageCD45RA T cellsT cell populationsBlood T cellsG2/M phaseNaive T cellsPhosphatase CD45Propidium iodide stainingHematopoietic cellsM phaseCD45RACD45RO isoformRestricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease.
Brod SA, Benjamin D, Hafler DA. Restricted T cell expression of IL-2/IFN-gamma mRNA in human inflammatory disease. The Journal Of Immunology 1991, 147: 810-5. PMID: 1907306, DOI: 10.4049/jimmunol.147.3.810.Peer-Reviewed Original ResearchConceptsPeripheral bloodCSF of subjectsIL-5 mRNAT cell clonesIFN-gamma mRNAIL-4Inflammatory diseasesIFN-gammaIL-2Systemic inflammationT cellsTh1 T cell clonesTh2-type T cellsT cell cytokine profilesIL-2/ILDistinct T cell populationsCell clonesT cell populationsT cell expressionType T cellsTNF-alpha mRNAHuman inflammatory diseasesIL-2 mRNACytokine profileImmune compartmentImmunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis
Hafler D, Orav J, Gertz R, Stazzone L, Weiner H. Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis. Journal Of Neuroimmunology 1991, 32: 149-158. PMID: 1672870, DOI: 10.1016/0165-5728(91)90007-t.Peer-Reviewed Original ResearchConceptsT cell populationsDisability Status ScaleMixed lymphocyte reactionSpontaneous proliferationT cellsImmune measuresACTH infusionImmune functionChronic progressive multiple sclerosisProgressive multiple sclerosis patientsCD4/CD8 ratioCell populationsAllogeneic mixed lymphocyte reactionFunctional immune measuresPeripheral blood CD4Progressive multiple sclerosisPositive clinical responsePositive T cellsMultiple sclerosis patientsFunctional immune assaysLevels of proliferationBlood CD4CD8 ratioClinical improvementClinical responseCommon T‐cell receptor Vβ usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis
Lee S, Wucherpfennig K, Brod S, Benjamin D, Weiner H, Hafler D. Common T‐cell receptor Vβ usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis. Annals Of Neurology 1991, 29: 33-40. PMID: 1847614, DOI: 10.1002/ana.410290109.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBase SequenceBlotting, SouthernChild, PreschoolClone CellsDNA ProbesFemaleGene Rearrangement, beta-Chain T-Cell Antigen ReceptorGene Rearrangement, gamma-Chain T-Cell Antigen ReceptorHumansMaleMiddle AgedMolecular Sequence DataMultiple SclerosisPhenotypePolymerase Chain ReactionT-LymphocytesConceptsT cell populationsT cell clonesCerebrospinal fluidMultiple sclerosisT cellsT cell receptor Vβ usageNeurological diseasesOligoclonal T-cell populationsT cell receptor V beta genesOligoclonal T lymphocytesOligoclonal T cellsSame T cell receptorBlood of patientsNormal control subjectsT cell receptor beta chainProgenitor T cellsT cell receptorIndividual T cellsGamma chain geneImmune compartmentVβ usageControl subjectsReceptor beta chainT lymphocytesPatients