2023
Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.
Song W, Sanchez G, Mayer D, Blackburn H, Chernova I, Flavell R, Weinstein J, Craft J. Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection. The Journal Of Immunology 2023, 210: 1861-1865. PMID: 37133336, PMCID: PMC10247523, DOI: 10.4049/jimmunol.2300027.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationInterleukinsLymphocytic ChoriomeningitisMiceMice, Inbred C57BLMice, KnockoutConceptsAge-associated B cellsIL-21Acute lymphocytic choriomeningitis virus infectionB cellsLymphocytic choriomeningitis virus infectionB cell activationHumoral immunityLymphoid organsVirus infectionMouse modelViral infectionB cell developmentCell activationLymphotoxin αVivo generationTissue-specific signalsInfectionDe novo generationOrgan contributionIFNTissue microenvironmentCell developmentLiverPivotal contributorStage-specific roles
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 functionCD4
2018
Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection
Xin G, Zander R, Schauder DM, Chen Y, Weinstein JS, Drobyski WR, Tarakanova V, Craft J, Cui W. Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection. Nature Communications 2018, 9: 5037. PMID: 30487586, PMCID: PMC6261948, DOI: 10.1038/s41467-018-07492-4.Peer-Reviewed Original ResearchConceptsCD4 T cellsIL-10Humoral immunityT cellsTfh cellsIL-10-expressing CD4 T cellsViral infectionAntiviral T cell responsesAcute LCMV infectionDouble reporter miceChronic viral infectionsCytokine IL-10T cell responsesPersistent viral infectionIL-10 signalingGerminal center reactionSingle-cell RNA-sequencing approachLCMV infectionHelper subsetsTh1 cellsChronic infectionInflammatory functionsViral controlPersistent infectionCell responses
2016
The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity
Chan PY, Carrera Silva EA, De Kouchkovsky D, Joannas LD, Hao L, Hu D, Huntsman S, Eng C, Licona-Limón P, Weinstein JS, Herbert DR, Craft JE, Flavell RA, Repetto S, Correale J, Burchard EG, Torgerson DG, Ghosh S, Rothlin CV. The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity. Science 2016, 352: 99-103. PMID: 27034374, PMCID: PMC4935984, DOI: 10.1126/science.aaf1358.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAsthmaBlood ProteinsDendritic CellsDisease Models, AnimalGene Knockout TechniquesHost-Parasite InteractionsHumansImmunity, InnateInterleukin-4MiceMice, Inbred C57BLMice, KnockoutNippostrongylusProtein SPyroglyphidaeReceptor Protein-Tyrosine KinasesStrongylida InfectionsT-LymphocytesConceptsType 2 immunityType 2 responsesType 2 cytokinesHuman dendritic cellsInnate immune cellsDendritic cellsAllergic diseasesImmune cellsT cellsAdaptive immunityInterleukin-4Host responseFunctional neutralizationGenetic ablationReceptor tyrosine kinasesImmunityProtective functionTyro3Tyrosine kinaseNegative regulatorPROS1CellsResponseCytokinesDisease
2015
IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells
Brodeur TY, Robidoux TE, Weinstein JS, Craft J, Swain SL, Marshak-Rothstein A. IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells. The Journal Of Immunology 2015, 195: 5251-5260. PMID: 26519529, PMCID: PMC4655158, DOI: 10.4049/jimmunol.1500777.Peer-Reviewed Original ResearchProduction of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells
Laidlaw BJ, Cui W, Amezquita RA, Gray SM, Guan T, Lu Y, Kobayashi Y, Flavell RA, Kleinstein SH, Craft J, Kaech SM. Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells. Nature Immunology 2015, 16: 871-879. PMID: 26147684, PMCID: PMC4713030, DOI: 10.1038/ni.3224.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD8-Positive T-LymphocytesDendritic CellsFlow CytometryGene Expression ProfilingHost-Pathogen InteractionsImmunologic MemoryInflammationInterleukin-10Lymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMice, Inbred C57BLMice, KnockoutReverse Transcriptase Polymerase Chain ReactionT-Lymphocytes, Regulatory
2014
CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection
Laidlaw BJ, Zhang N, Marshall HD, Staron MM, Guan T, Hu Y, Cauley LS, Craft J, Kaech SM. CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection. Immunity 2014, 41: 633-645. PMID: 25308332, PMCID: PMC4324721, DOI: 10.1016/j.immuni.2014.09.007.Peer-Reviewed Original ResearchConceptsT cellsTRM cellsT-betTissue-resident memory T cellsLung-resident memory CD8T cell-dependent signalsT cell-derived interferonTranscription factor T-betLung Trm cellsMemory T cellsInfluenza viral infectionInfluenza virus infectionT cell helpHeterosubtypic challengeCD103 expressionMemory CD8Respiratory infectionsMucosal sitesCell helpAirway epitheliumVirus infectionViral infectionInfectionLung airwaysImpaired abilityDynamic signaling by T follicular helper cells during germinal center B cell selection
Shulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft JE, Nussenzweig MC. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 2014, 345: 1058-1062. PMID: 25170154, PMCID: PMC4519234, DOI: 10.1126/science.1257861.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsGerminal centersAntibody-producing B cellsCytokine interleukin-4B cell selectionGerminal center B cell selectionInterleukin-4Transient elevationMajor histocompatibilitySustained increaseFree calciumClonal expansionCognate peptideIntravital imagingCell migrationCellsIntracellularCell selectionHigh levelsHistocompatibilityB Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen
Weinstein JS, Bertino SA, Hernandez SG, Poholek AC, Teplitzky TB, Nowyhed HN, Craft J. B Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen. The Journal Of Immunology 2014, 192: 3166-3179. PMID: 24610013, PMCID: PMC3991608, DOI: 10.4049/jimmunol.1302617.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAntigens, CD19B-LymphocytesCell ProliferationDNA-Binding ProteinsFlow CytometryInducible T-Cell Co-Stimulator LigandMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, ConfocalNitrophenolsOvalbuminPhenylacetatesProto-Oncogene Proteins c-bcl-6Reverse Transcriptase Polymerase Chain ReactionT-LymphocytesT-Lymphocytes, Helper-InducerConceptsCognate B cellsTfh cell developmentB cellsICOS ligandFollicular Th cell developmentCell developmentNoncognate B cellsFollicular helper cell developmentTfh cell differentiationAg-specific B cellsICOS-L expressionB cell expressionTh cell developmentGerminal center differentiationICOS blockadeTfh cellsAg deliverySystemic autoimmunityCell expressionCell maturationICOSCellsDeliveryCell differentiationCells displayTranscription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells
Ray JP, Marshall HD, Laidlaw BJ, Staron MM, Kaech SM, Craft J. Transcription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells. Immunity 2014, 40: 367-377. PMID: 24631156, PMCID: PMC3992517, DOI: 10.1016/j.immuni.2014.02.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralAntibody SpecificityB-LymphocytesCD4 AntigensCD4-Positive T-LymphocytesCell DifferentiationGene Expression ProfilingGene Expression RegulationGerminal CenterImmunoglobulin Class SwitchingInterferon Type ILymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMiceMice, KnockoutSignal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorT-Lymphocytes, Helper-InducerTranscriptomeConceptsTfh cellsType I interferonI interferonViral infectionFollicular helper T cellsT helper 1 cellsAntigen-specific antibody productionGC B cell phenotypeHigh affinity antibody-secreting cellsTfh cell differentiationHelper T cellsB cell memoryLymphocytic choriomeningitis virusB-cell phenotypeAntibody-secreting cellsGerminal center B cellsEffector phenotypeReceptor blockadeAcute infectionFollicular helperIFN-inducible genesT cellsTranscription factor STAT3B cellsAntibody production
2012
IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice
Rankin AL, Guay H, Herber D, Bertino SA, Duzanski TA, Carrier Y, Keegan S, Senices M, Stedman N, Ryan M, Bloom L, Medley Q, Collins M, Nickerson-Nutter C, Craft J, Young D, Dunussi-Joannopoulos K. IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice. The Journal Of Immunology 2012, 188: 1656-1667. PMID: 22231702, PMCID: PMC3618484, DOI: 10.4049/jimmunol.1003871.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoimmunityB-LymphocytesCD4-Positive T-LymphocytesCell DifferentiationInterferon-gammaInterleukinsLupus Erythematosus, SystemicLymphatic DiseasesLymphocyte ActivationMiceMice, Inbred MRL lprMice, KnockoutReceptors, Interleukin-21SkinSplenomegalyT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerConceptsT cell effector subsetsIL-21Effector subsetsIL-21RT cellsHelper cellsSpontaneous germinal center formationIL-21-dependent mannerIL-21 receptorMRL/MpJPlasma cell accumulationGerminal center formationTh cell differentiationSignificant reductionAutoantibody titersAutoantibody productionCytokines IFNImmune activationSystemic autoimmunityJ miceDisease manifestationsT lymphocytesPleiotropic cytokineB cellsDisease pathogenesis
2011
An Interleukin-21- Interleukin-10-STAT3 Pathway Is Critical for Functional Maturation of Memory CD8+ T Cells
Cui W, Liu Y, Weinstein JS, Craft J, Kaech SM. An Interleukin-21- Interleukin-10-STAT3 Pathway Is Critical for Functional Maturation of Memory CD8+ T Cells. Immunity 2011, 35: 792-805. PMID: 22118527, PMCID: PMC3431922, DOI: 10.1016/j.immuni.2011.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationGene Expression Regulation, DevelopmentalImmunologic MemoryInterleukin-10InterleukinsMiceMice, KnockoutPositive Regulatory Domain I-Binding Factor 1Proto-Oncogene Proteins c-bcl-6Signal TransductionSTAT3 Transcription FactorSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsT-Box Domain ProteinsTranscription FactorsConceptsMemory T cellsT cellsBCL-6Protective memory T cellsCentral memory T cellsSTAT3 pathwayAcute LCMV infectionExpression of EomesLong-term immunityMemory precursor cellsSTAT3-SOCS3 pathwayMemory cell developmentCell developmentT cell developmentMemory CD8IL-21LCMV infectionIL-12Interleukin-10Inflammatory cytokinesFunctional maturationSOCS3 expressionBlimp-1Precursor cellsSTAT3The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ. The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice. Science 2011, 332: 478-484. PMID: 21393509, PMCID: PMC3104397, DOI: 10.1126/science.1199214.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsAnti-Inflammatory Agents, Non-SteroidalArthritis, ExperimentalCartilage, ArticularFemaleGranulinsHumansIntercellular Signaling Peptides and ProteinsLigandsMaleMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMiddle AgedProgranulinsProtein Interaction Domains and MotifsReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionT-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaYoung AdultConceptsInflammatory arthritisAdministration of progranulinAntagonist of TNFαCollagen-induced arthritisArthritis mouse modelPGRN-deficient miceNew potential therapeutic interventionsPotential therapeutic interventionsGrowth factor progranulinNecrosis factor receptorRheumatoid arthritisMouse modelArthritisTherapeutic interventionsProgranulinTNF receptorFactor receptorMiceReceptorsInflammationTissue repairTNFαIntracellular signalingAtsttrinTNFR
2010
In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development
Poholek AC, Hansen K, Hernandez SG, Eto D, Chandele A, Weinstein JS, Dong X, Odegard JM, Kaech SM, Dent AL, Crotty S, Craft J. In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development. The Journal Of Immunology 2010, 185: 313-326. PMID: 20519643, PMCID: PMC2891136, DOI: 10.4049/jimmunol.0904023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CommunicationCell DifferentiationCricetinaeDNA-Binding ProteinsDown-RegulationFemaleImmunophenotypingLymphocyte CooperationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicProto-Oncogene Proteins c-bcl-6SpleenT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerUp-RegulationConceptsPD-1 upregulationIL-21IL-6B cellsFollicular helper T cellsFollicular helper cell developmentDeath receptor-1Helper T cellsCytokines IL-6B cell interactionsB cell maturationTranscriptional repressor BCL6Vivo regulationCell developmentP-selectin glycoprotein ligand-1New surface markersT cellsGerminal centersInitial upregulationReceptor 1CXCR5BCL6 upregulationCell maturationSurface markersBCL6 expressionNaturally Activated Vγ4 γδ T Cells Play a Protective Role in Tumor Immunity through Expression of Eomesodermin
He W, Hao J, Dong S, Gao Y, Tao J, Chi H, Flavell R, O’Brien R, Born WK, Craft J, Han J, Wang P, Zhao L, Wu J, Yin Z. Naturally Activated Vγ4 γδ T Cells Play a Protective Role in Tumor Immunity through Expression of Eomesodermin. The Journal Of Immunology 2010, 185: 126-133. PMID: 20525896, PMCID: PMC3813958, DOI: 10.4049/jimmunol.0903767.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell Line, TumorCoculture TechniquesCytotoxicity, ImmunologicHyaluronan ReceptorsInterferon-gammaLymphocyte ActivationMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPerforinReceptors, Antigen, T-Cell, gamma-deltaT-Box Domain ProteinsT-Lymphocyte SubsetsUp-RegulationConceptsGammadelta T cellsAntitumor immune responseT cellsImmune responseIFN-gammaTumor immunityProtective roleVγ4 γδ T cellsTumor immune surveillanceΓδ T cellsIFN-gamma secretionTumor immune therapyMore IFN-gammaGreater cytolytic activityExpression of EomesoderminAntitumor responseImmune therapyImmune surveillanceCytolytic activityEffector functionsPrincipal subsetsVgamma4Vgamma1Precise rolePerforin
2008
ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity
Odegard JM, Marks BR, DiPlacido LD, Poholek AC, Kono DH, Dong C, Flavell RA, Craft J. ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. Journal Of Experimental Medicine 2008, 205: 2873-2886. PMID: 18981236, PMCID: PMC2585848, DOI: 10.1084/jem.20080840.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteAutoimmunityCell DifferentiationChemokinesDisease Models, AnimalGerminal CenterImmunoglobulin Class SwitchingImmunoglobulin GInducible T-Cell Co-Stimulator ProteinInterleukinsLupus Erythematosus, SystemicMembrane GlycoproteinsMiceMice, KnockoutPlasma CellsReceptors, CXCR4T-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerConceptsEffector T cellsT cellsIL-21IgG productionCXC chemokine receptor 4 (CXCR4) expressionB cell helper functionFollicular helper T cellsChemokine receptor 4 expressionReceptor 4 expressionCD4 T cellsHelper T cellsMRL/MpJAutoimmune strainsP-selectin glycoprotein ligand-1Autoantibody productionChronic autoimmunitySystemic autoimmunityPlasma cellsExtrafollicular responseExtrafollicular sitesMouse modelGerminal centersHelper functionSelective lossLigand 1
2007
Epigenetic and Transcriptional Programs Lead to Default IFN-γ Production by γδ T Cells
Chen L, He W, Kim ST, Tao J, Gao Y, Chi H, Intlekofer AM, Harvey B, Reiner SL, Yin Z, Flavell RA, Craft J. Epigenetic and Transcriptional Programs Lead to Default IFN-γ Production by γδ T Cells. The Journal Of Immunology 2007, 178: 2730-2736. PMID: 17312115, DOI: 10.4049/jimmunol.178.5.2730.Peer-Reviewed Original Research
2006
γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice
Wang T, Gao Y, Scully E, Davis CT, Anderson JF, Welte T, Ledizet M, Koski R, Madri JA, Barrett A, Yin Z, Craft J, Fikrig E. γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice. The Journal Of Immunology 2006, 177: 1825-1832. PMID: 16849493, DOI: 10.4049/jimmunol.177.3.1825.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD8-Positive T-LymphocytesGenetic Predisposition to DiseaseImmunity, CellularImmunity, InnateImmunization, SecondaryImmunoglobulin GImmunoglobulin MImmunologic MemoryLymphocyte DepletionMiceMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaRecurrenceT-Lymphocyte SubsetsWest Nile FeverWest Nile virusConceptsGammadelta T cellsWild-type miceT cellsWN virus infectionPrimary infectionVirus infectionWN virusNaive miceSecondary challengeImmune responseAdaptive immunityCD8 memory T cellsWest Nile virus infectionMemory T cellsProtective immune responseAdaptive immune responsesAdoptive transferWest Nile virusAb responsesLethal infectionViral challengeFatal meningoencephalitisSecondary infectionInfectionMice
2005
Role for macrophage migration inhibitory factor in asthma
Mizue Y, Ghani S, Leng L, McDonald C, Kong P, Baugh J, Lane SJ, Craft J, Nishihira J, Donnelly SC, Zhu Z, Bucala R. Role for macrophage migration inhibitory factor in asthma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 14410-14415. PMID: 16186482, PMCID: PMC1242335, DOI: 10.1073/pnas.0507189102.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAsthmaBase SequenceBronchoalveolar LavageCell ProliferationCells, CulturedCytokinesEnzyme-Linked Immunosorbent AssayFlow CytometryGene ComponentsGenotypeHumansInterleukin-5Intramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceMice, Inbred BALB CMice, KnockoutOvalbuminReverse Transcriptase Polymerase Chain ReactionT-Lymphocytes, Helper-InducerConceptsMacrophage migration inhibitory factorMigration inhibitory factorInhibitory factorIL-5 concentrationsLower airway hyperresponsivenessBronchoalveolar lavage fluidAntigen-specific responsesT-cell studiesWild-type miceLess pulmonary inflammationAirway hyperresponsivenessImmunologic regulatorsMIF deficiencyMIF KOMIF's roleMild asthmaWild-type controlsSevere asthmaAsthma patientsCytokine levelsMIF genotypePulmonary inflammationSpecific IgEWhite patientsAutoimmune disordersNaive CD4+ T Cells from Lupus-Prone Fas-Intact MRL Mice Display TCR-Mediated Hyperproliferation Due to Intrinsic Threshold Defects in Activation
Zielinski CE, Jacob SN, Bouzahzah F, Ehrlich BE, Craft J. Naive CD4+ T Cells from Lupus-Prone Fas-Intact MRL Mice Display TCR-Mediated Hyperproliferation Due to Intrinsic Threshold Defects in Activation. The Journal Of Immunology 2005, 174: 5100-5109. PMID: 15814741, DOI: 10.4049/jimmunol.174.8.5100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAutoimmunityCalcium SignalingCD4-Positive T-LymphocytesCell ProliferationColumbidaeCytochromes cDendritic CellsFas ReceptorGenes, DominantInterleukin-2Lupus Erythematosus, SystemicLymphocyte ActivationMiceMice, Inbred MRL lprMice, Inbred StrainsMice, KnockoutMice, TransgenicPhenotypeReceptor-CD3 Complex, Antigen, T-CellReceptors, Antigen, T-CellSignal TransductionConceptsNaive CD4T cellsSelf-AgAutoreactive T cell activationMRL T cellsT cell toleranceF1 T cellsProximal defectsAnti-CD3 stimulationClass II MHCIL-2 productionT cell activationWild-type CD4Pigeon cytochrome cCell calcium signalingDendritic cellsControl miceMurine lupusObserved hyperactivityII MHCMRL miceIntracellular calciumLow thresholdPeptide AgCD4