2021
Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study
, , Rouphael N, Maecker H, Montgomery R, Diray-Arce J, Kleinstein S, Altman M, Bosinger S, Eckalbar W, Guan L, Hough C, Krammer F, Langelier C, Levy O, McEnaney K, Peters B, Rahman A, Rajan J, Sigelman S, Steen H, van Bakel H, Ward A, Wilson M, Woodruff P, Zamecnik C, Augustine A, Ozonoff A, Reed E, Becker P, Higuita N, Altman M, Atkinson M, Baden L, Becker P, Bime C, Brakenridge S, Calfee C, Cairns C, Corry D, Davis M, Augustine A, Ehrlich L, Haddad E, Erle D, Fernandez-Sesma A, Hafler D, Hough C, Kheradmand F, Kleinstein S, Kraft M, Levy O, McComsey G, Melamed E, Messer W, Metcalf J, Montgomery R, Nadeau K, Ozonoff A, Peters B, Pulendran B, Reed E, Rouphael N, Sarwal M, Schaenman J, Sekaly R, Shaw A, Simon V. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study. Science Immunology 2021, 6: eabf3733. PMID: 34376480, PMCID: PMC8713959, DOI: 10.1126/sciimmunol.abf3733.Peer-Reviewed Original ResearchConceptsCOVID-19 cohortProspective longitudinal studyHost immune responseLongitudinal studyCOVID-19Identification of biomarkersHospitalized patientsRespiratory secretionsClinical criteriaDisease progressionImmune responseRadiographic dataImmunologic assaysEffective therapeuticsOptimal timingStudy designBiologic samplingSuch interventionsCohortSeveritySample collectionAssay protocolsPatientsSingle cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signs
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
2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cells
2011
Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis
Raddassi K, Kent SC, Yang J, Bourcier K, Bradshaw EM, Seyfert-Margolis V, Nepom GT, Kwok WW, Hafler DA. Increased Frequencies of Myelin Oligodendrocyte Glycoprotein/MHC Class II-Binding CD4 Cells in Patients with Multiple Sclerosis. The Journal Of Immunology 2011, 187: 1039-1046. PMID: 21653833, PMCID: PMC3131477, DOI: 10.4049/jimmunol.1001543.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAmino Acid SubstitutionCD4 Lymphocyte CountCD4-Positive T-LymphocytesCell CommunicationCell Line, TransformedCells, CulturedEpitopes, T-LymphocyteFemaleGene FrequencyHLA-DR AntigensHLA-DRB1 ChainsHumansImmunophenotypingMaleMiddle AgedMultiple SclerosisMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsProtein BindingProtein MultimerizationConceptsMyelin-reactive T cellsMultiple sclerosisT cell clonesT cellsHealthy controlsMOG-reactive T cellsAutoantigen-specific T cellsCell clonesStimulation of PMBCsClass II tetramersPathogenic immune cellsReactive T cellsSpecific T cellsMyelin oligodendrocyte glycoproteinHLA class IIBlood of subjectsT-cell cloning techniqueMOG peptidesShort-term cultureCD4 cellsMS subjectsAutoimmune diseasesPeripheral bloodControl subjectsOligodendrocyte glycoprotein
2008
Cytometric profiling in multiple sclerosis uncovers patient population structure and a reduction of CD8low cells
De Jager PL, Rossin E, Pyne S, Tamayo P, Ottoboni L, Viglietta V, Weiner M, Soler D, Izmailova E, Faron-Yowe L, O’Brien C, Freeman S, Granados S, Parker A, Roubenoff R, Mesirov JP, Khoury SJ, Hafler DA, Weiner HL. Cytometric profiling in multiple sclerosis uncovers patient population structure and a reduction of CD8low cells. Brain 2008, 131: 1701-1711. PMID: 18567923, PMCID: PMC2730047, DOI: 10.1093/brain/awn118.Peer-Reviewed Original ResearchConceptsRelapsing-remitting MSImmunological profileRRMS subjectsPeripheral bloodUntreated subjectsNatural killer cell profileComprehensive Longitudinal InvestigationAbsence of treatmentCell surface markersCIS subjectsDemyelinating diseaseDemyelination syndromeWomen's HospitalHealthy controlsCytometric profilingCell profilesMonoclonal antibodiesExtension phaseFresh bloodBiomarker discovery effortsDistinct subsetsBloodCell populationsGating strategyHospital
2005
Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells
Baecher-Allan C, Wolf E, Hafler DA. Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells. Clinical Immunology 2005, 115: 10-18. PMID: 15870015, DOI: 10.1016/j.clim.2005.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, B-LymphocyteCD4-Positive T-LymphocytesCD58 AntigensCoculture TechniquesEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingL-SelectinLeukocyte Common AntigensReceptors, Interleukin-2Receptors, TransferrinT-Lymphocyte SubsetsConceptsCD4 T cellsT cellsTreg cellsRegulatory cellsTotal CD4 T cellsHuman regulatory cellsRegulatory T cellsAutoimmune disease modelsImportance of CD4Regulatory populationImmune homeostasisCD25Suppressive activityCD4Human regulatorySpecific subpopulationsDisease modelsSignificant proportionMiceVivoMurine cellsPotential heterogeneityFuture studiesCellsHuman diseases
2001
Immunological Memory: Contribution of Memory B Cells Expressing Costimulatory Molecules in the Resting State
Bar-Or A, Oliveira E, Anderson D, Krieger J, Duddy M, O’Connor K, Hafler D. Immunological Memory: Contribution of Memory B Cells Expressing Costimulatory Molecules in the Resting State. The Journal Of Immunology 2001, 167: 5669-5677. PMID: 11698439, DOI: 10.4049/jimmunol.167.10.5669.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell subsetsB cellsCell subsetsCostimulatory moleculesB cell memory compartmentMemory responsesImmune memory responseDistinct B cell subsetsHuman memory B cellsHumoral memory responsesHuman B cellsTh cellsImmunological memoryT cellsMemory compartmentPoor APCsMurine systemNovel subpopulationRelative paucityCellsIn vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG
Ohashi T, Yukitake M, Slavin A, Krieger J, Hafler D. In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG. Journal Of Neuroimmunology 2001, 118: 194-202. PMID: 11498254, DOI: 10.1016/s0165-5728(01)00321-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibody SpecificityBlotting, WesternCell LineClone CellsCytokinesElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingImmunosorbent TechniquesLymphocyte ActivationMiceMultiple SclerosisMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinSensitivity and SpecificityT-Lymphocytes
2000
A 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 subjectsPatients
1999
Noncanonical Vα24JαQ T cells with conservative α chain CDR3 region amino acid substitutions are restricted by CD1d
Kent S, Hafler D, Strominger J, Wilson S. Noncanonical Vα24JαQ T cells with conservative α chain CDR3 region amino acid substitutions are restricted by CD1d. Human Immunology 1999, 60: 1080-1089. PMID: 10600006, DOI: 10.1016/s0198-8859(99)00109-3.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, CD1Antigens, CD1dBase SequenceClone CellsComplementarity Determining RegionsConserved SequenceDNAGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorHumansImmunoglobulin Variable RegionImmunophenotypingKiller Cells, NaturalReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsConceptsT cell receptorT cellsCD1d restrictionPeripheral blood mononuclear cellsBlood mononuclear cellsAmino acid substitutionsAlpha chainSingle amino acid substitutionHuman CD161Total CD4Mononuclear cellsInterleukin-4Surface phenotypeRestriction elementsCD4Acid substitutionsCD1dCDR3 residuesJ rearrangementsJ junctionsVariant clonesChain transcriptsCellsJalpha18Valpha24
1995
Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. Journal Of Experimental Medicine 1995, 182: 1985-1996. PMID: 7500044, PMCID: PMC2192240, DOI: 10.1084/jem.182.6.1985.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsMultiple sclerosisT cellsB7-1Autoimmune diseasesCostimulatory moleculesMS plaquesB7-2T cell-mediated autoimmune diseaseInitiation of MSMyelin-autoreactive T cellsCell-mediated autoimmune diseaseSelf-reactive T cellsCostimulatory molecules B7-1Acute MS plaquesAutoimmune animal modelsInterleukin-12 cytokinesPutative autoimmune diseaseSemiquantitative reverse transcriptase-polymerase chain reactionReverse transcriptase-polymerase chain reactionExpression of cytokinesTranscriptase-polymerase chain reactionT cell activationMultiple sclerosis lesionsInflammatory cuffs
1991
Restricted 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 compartment
1990
T‐T cell interactions are mediated by adhesion molecules
Brod S, Purvee M, Benjamin D, Hafler D. T‐T cell interactions are mediated by adhesion molecules. European Journal Of Immunology 1990, 20: 2259-2268. PMID: 1700751, DOI: 10.1002/eji.1830201015.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, Differentiation, T-LymphocyteAntigens, SurfaceCD3 ComplexCD58 AntigensCell Adhesion MoleculesCell CommunicationClone CellsHumansImmunophenotypingInterleukin-2Lymphocyte ActivationLymphocyte Function-Associated Antigen-1Membrane GlycoproteinsMitogensReceptors, Antigen, T-CellT-LymphocytesConceptsT cell clonesAutologous T cell clonesPeripheral blood T cellsAdhesion molecules LFA-1Blood T cellsT cellsLFA-3Major histocompatibility complexInflammatory responseCell clonesICAM-1LFA-1T cell immune functionCD3/T cell receptor complexSpecific T cellsCell adhesion molecules LFA-1Cell immune functionT cell interactionsT cell activationT cell receptor complexMHC determinantsCell receptor complexImmune functionCell activationCD2 pathway