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 ResearchMeSH KeywordsCD4-Positive T-LymphocytesCOVID-19HumansPlasma CellsProgrammed Cell Death 1 ReceptorReceptors, CXCR3Receptors, CXCR5T-Lymphocytes, Helper-InducerConceptsAcute 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
2022
Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis
Asashima H, Axisa PP, Pham THG, Longbrake EE, Ruff WE, Lele N, Cohen I, Raddassi K, Sumida TS, Hafler DA. Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis. Journal Of Clinical Investigation 2022, 132: e156254. PMID: 36250467, PMCID: PMC9566906, DOI: 10.1172/jci156254.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCD40 LigandCell ProliferationHumansInterleukin-17LigandsMultiple SclerosisReceptors, ImmunologicT Follicular Helper CellsT-Lymphocytes, Helper-InducerTranscription FactorsConceptsRelapsing-remitting multiple sclerosisMemory B cellsCTfh cellsB cellsTIGIT expressionMultiple sclerosisT cellsFollicular helper T cellsHealthy age-matched controlsB-cell depletionT cell expansionHelper T cellsAge-matched controlsB cell functionB-cell pathwayDifferential gene expression signaturesTfh cellsDisease activityGene expression signaturesCell depletionCD40 ligandTranscription factor TCF4Disease pathogenesisImmune systemNew MRI
2013
Role of “Western Diet” in Inflammatory Autoimmune Diseases
Manzel A, Muller DN, Hafler DA, Erdman SE, Linker RA, Kleinewietfeld M. Role of “Western Diet” in Inflammatory Autoimmune Diseases. Current Allergy And Asthma Reports 2013, 14: 404. PMID: 24338487, PMCID: PMC4034518, DOI: 10.1007/s11882-013-0404-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesComorbidityDietFeeding BehaviorHumansInflammationIntestinal MucosaLife StyleMicrobiotaObesityT-Lymphocytes, Helper-InducerConceptsAutoimmune diseasesWestern dietInflammatory autoimmune diseaseExcess salt intakeImmunologic mechanismsMetabolic syndromeSalt intakeAutoimmune pathologyCardiovascular diseaseT cellsWesternized countriesFrequent consumptionDietary influencesInfectious diseasesDiseaseNutritional patternsFast foodPathogen exposureDietCurrent knowledgeCentral playerAutoimmunityObesitySyndromeCholesterolThe 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 approachesMicrobial Reprogramming Inhibits Western Diet-Associated Obesity
Poutahidis T, Kleinewietfeld M, Smillie C, Levkovich T, Perrotta A, Bhela S, Varian BJ, Ibrahim YM, Lakritz JR, Kearney SM, Chatzigiagkos A, Hafler DA, Alm EJ, Erdman SE. Microbial Reprogramming Inhibits Western Diet-Associated Obesity. PLOS ONE 2013, 8: e68596. PMID: 23874682, PMCID: PMC3707834, DOI: 10.1371/journal.pone.0068596.Peer-Reviewed Original ResearchConceptsAge-associated weight gainWeight gainT cellsFast foodAd libitum caloric intakeActive immune toleranceImmune cell profilesRegulatory T cellsT cell balanceRecent epidemiological studiesLikelihood of obesityNaïve recipient animalsGut microbial ecologyT helperImmune toleranceBaseline dietWeight managementCaloric intakePopulation-based approachMouse modelCell balanceEpidemiological studiesRecipient animalsAnimal modelsAbdominal fat
2010
TGF-β Induces IL-9 Production from Human Th17 Cells
Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA. TGF-β Induces IL-9 Production from Human Th17 Cells. The Journal Of Immunology 2010, 185: 46-54. PMID: 20498357, PMCID: PMC2936106, DOI: 10.4049/jimmunol.1000356.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell PolarityCells, CulturedCoculture TechniquesDiabetes Mellitus, Type 1Gene Expression RegulationHumansImmunohistochemistryInflammation MediatorsInterleukin-17Interleukin-9Middle AgedResting Phase, Cell CycleT-Lymphocytes, Helper-InducerTransforming Growth Factor beta1Young AdultConceptsCD4 T cellsIL-9 productionIL-17IL-9IL-1betaCD4 cellsProinflammatory cytokinesT cellsNaive cellsIL-9/ILCD4 T cell subsetsMemory CD4 T cellsNaive CD4 T cellsHuman naive CD4 T cellsTh17-inducing cytokinesT cell subsetsHuman autoimmune diseasesAutoimmune diabetesMemory CD4Th17 cellsTh2 cytokinesAutoimmune diseasesCell subsetsIL-4Inflammatory conditions
2009
TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines
Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. European Journal Of Immunology 2009, 39: 2492-2501. PMID: 19676072, PMCID: PMC2759376, DOI: 10.1002/eji.200939274.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCD4-Positive T-LymphocytesCytokinesGalectinsHepatitis A Virus Cellular Receptor 2HumansImmunologic FactorsMembrane ProteinsTh1 CellsT-Lymphocytes, Helper-Inducer
2008
IL-21 and TGF-β are required for differentiation of human TH17 cells
Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA. IL-21 and TGF-β are required for differentiation of human TH17 cells. Nature 2008, 454: 350-352. PMID: 18469800, PMCID: PMC2760130, DOI: 10.1038/nature07021.Peer-Reviewed Original Research
2007
Protective and therapeutic role for αB-crystallin in autoimmune demyelination
Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O’Conner K, Hafler DA, Sobel RA, Robinson WH, Steinman L. Protective and therapeutic role for αB-crystallin in autoimmune demyelination. Nature 2007, 448: 474-479. PMID: 17568699, DOI: 10.1038/nature05935.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAnimalsAutoimmunityCell DifferentiationCytokinesHumansMultiple SclerosisT-Lymphocyte SubsetsT-Lymphocytes, Helper-Inducer
1996
Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients.
Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. Journal Of Clinical Investigation 1996, 98: 70-77. PMID: 8690806, PMCID: PMC507402, DOI: 10.1172/jci118779.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cellsOral administrationAutoimmune diseasesTetanus toxoidT cell linesMS patientsMultiple sclerosisProteolipid proteinFrequency of MBPNon-treated MS patientsPLP-reactive T cellsTh1-type autoimmune diseaseShort-term T cell linesCell-mediated autoimmune diseaseRelapsing-remitting MS patientsOriginal T cell cloneSpecific IFN-gammaSystemic immune toleranceExperimental autoimmune diseasesRegulatory T cellsReactive T cellsIFN-gamma secretionMultiple sclerosis patientsT cell clones
1989
Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid
Chofflon M, Weiner H, Morimoto C, Hafler D. Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid. Annals Of Neurology 1989, 25: 494-499. PMID: 2528316, DOI: 10.1002/ana.410250512.Peer-Reviewed Original ResearchConceptsInducer T cellsSuppressor-inducer T cellsMultiple sclerosis patientsT cellsCerebrospinal fluidMultiple sclerosisPeripheral bloodSclerosis patientsInducer cellsInducer functionMultiple sclerosis cerebrospinal fluidHelper-inducer T cellsCentral nervous system compartmentHelper inducer functionHelper-inducer cellsLocal autoimmune processesSuppressor-inducer functionSuppressor-inducer cellsCentral nervous systemSamples of bloodFlow cytometric analysisHelper inducerAutoimmune processInflammatory disordersT lymphocytes
1988
Immunohistochemical Analysis of Suppressor‐Inducer and Helper‐Inducer T Cells in Multiple Sclerosis Brain Tissue
SOBEL R, HAFLER D, CASTRO E, MORIMOTO C, WEINER H. Immunohistochemical Analysis of Suppressor‐Inducer and Helper‐Inducer T Cells in Multiple Sclerosis Brain Tissue. Annals Of The New York Academy Of Sciences 1988, 540: 306-308. PMID: 2905121, DOI: 10.1111/j.1749-6632.1988.tb27082.x.Peer-Reviewed Original ResearchLoss of Functional Suppression Is Linked to Decreases in Circulating Suppressor‐Inducer (CD4+2H4+) T Cells in Multiple Sclerosis
CHOFFLON M, WEINER H, HAFLER D. Loss of Functional Suppression Is Linked to Decreases in Circulating Suppressor‐Inducer (CD4+2H4+) T Cells in Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1988, 540: 330-332. PMID: 2905122, DOI: 10.1111/j.1749-6632.1988.tb27089.x.Peer-Reviewed Original Research
1987
Selective Loss of the Suppressor-Inducer T-Cell Subset in Progressive Multiple Sclerosis
Morimoto C, Hafler D, Weiner H, Letvin N, Hagan M, Daley J, Schlossman S. Selective Loss of the Suppressor-Inducer T-Cell Subset in Progressive Multiple Sclerosis. New England Journal Of Medicine 1987, 316: 67-72. PMID: 2946956, DOI: 10.1056/nejm198701083160202.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalFemaleFlow CytometryHumansImmunoglobulin GLymphocytesMaleMiddle AgedMultiple SclerosisT-Lymphocytes, Helper-InducerT-Lymphocytes, RegulatoryConceptsProgressive multiple sclerosisMultiple sclerosisStable diseaseHealthy controlsT cellsNeurologic diseaseSuppressor-inducer T cell subsetPeripheral blood lymphocyte subsetsSelective decreaseCubic millimeterPeripheral blood T cellsAnti-2H4 antibodySuppressor T cellsSuppressor T lymphocytesT cell subsetsPercentage of reactivityProduction of IgGCentral nervous systemDual-color fluorescence analysisPolymorphic antigenic determinantsActivation of cellsAnti-2H4Lymphocyte subsetsAcute attacksSuppressor cells