Featured Publications
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K
Lucas CL, Zhang Y, Venida A, Wang Y, Hughes J, McElwee J, Butrick M, Matthews H, Price S, Biancalana M, Wang X, Richards M, Pozos T, Barlan I, Ozen A, Rao VK, Su HC, Lenardo MJ. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. Journal Of Experimental Medicine 2014, 211: 2537-2547. PMID: 25488983, PMCID: PMC4267241, DOI: 10.1084/jem.20141759.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlternative SplicingAntibody FormationBase SequenceCatalytic DomainCD8-Positive T-LymphocytesCell DifferentiationChild, PreschoolClass Ia Phosphatidylinositol 3-KinaseEnzyme ActivationExonsFemaleGenes, DominantHeterozygoteHumansImmunologic Deficiency SyndromesLymphoproliferative DisordersMaleMolecular Sequence DataMutationPedigreePhosphatidylinositol 3-KinasesProtein Structure, TertiarySequence DeletionSignal TransductionTelomereTOR Serine-Threonine KinasesConceptsT cellsPI3KPI3K subunitsSenescent T cellsRecurrent sinopulmonary infectionsHeterozygous splice site mutationSplice site mutationEffector cellsPeripheral bloodSinopulmonary infectionsHuman immunodeficiencyHeterozygous splice mutationsImmunodeficiency diseaseHealthy subjectsUnique disorderHeterozygous mutationsClass IaPatient cellsProminent expansionK subunitLymphoproliferationPatientsSimilar diseasesShort telomeresDisease
2013
Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D
Chaigne-Delalande B, Li FY, O’Connor G, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection Through NKG2D. Science 2013, 341: 186-191. PMID: 23846901, PMCID: PMC3894782, DOI: 10.1126/science.1240094.Peer-Reviewed Original ResearchConceptsEpstein-Barr virusNatural killerMagnesium transporter 1T cellsChronic EBV infectionCD8 T cellsIntracellular free magnesium concentrationEBV infectionCytolytic responsesCytotoxic functionReceptor NKG2DMagnesium supplementationBasal intracellularAntiviral immunityCytolytic activityFree magnesium concentrationNKG2DTransporter 1Genetic deficiencyDefective expressionCritical regulatorMagnesium concentrationKillerCellsIntracellular
2011
LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L
Lucas CL, Workman CJ, Beyaz S, LoCascio S, Zhao G, Vignali DA, Sykes M. LAG-3, TGF-β, and cell-intrinsic PD-1 inhibitory pathways contribute to CD8 but not CD4 T-cell tolerance induced by allogeneic BMT with anti-CD40L. Blood 2011, 117: 5532-5540. PMID: 21422469, PMCID: PMC3109721, DOI: 10.1182/blood-2010-11-318675.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigens, CDAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenBone Marrow TransplantationCD4-Positive T-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCTLA-4 AntigenFemaleImmune ToleranceLymphocyte Activation Gene 3 ProteinMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalPeptidesProgrammed Cell Death 1 Ligand 2 ProteinProgrammed Cell Death 1 ReceptorSignal TransductionTransforming Growth Factor betaTransplantation, HomologousConceptsT cell toleranceCD4 T cell tolerancePeripheral CD8PD-1LAG-3T cellsCD8 T cell tolerance inductionPD-1/PD-L1 pathwayCD8 T cell tolerancePD-1 inhibitory pathwayT cell tolerance inductionAdoptive transfer studiesAllogeneic BM transplantationPD-L1 pathwayAlloreactive T cellsMixed hematopoietic chimerismT cell-intrinsic requirementB7.1/B7.2Cell-intrinsic requirementTGF-β signalingAllogeneic BMTPD-L1Mixed chimerasPD-L2Tolerance induction
2009
A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo
Fehr T, Lucas CL, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A, Sykes M. A CD8 T cell–intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 2009, 115: 1280-1287. PMID: 20007805, PMCID: PMC2826238, DOI: 10.1182/blood-2009-07-230680.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalApoptosis Regulatory ProteinsBone Marrow TransplantationCalcineurinCD4-Positive T-LymphocytesCD40 LigandCD8-Positive T-LymphocytesCyclosporineFemaleFlow CytometryGraft SurvivalImmune ToleranceMiceMice, Inbred C57BLMice, TransgenicNFATC Transcription FactorsReceptors, Antigen, T-CellSignal TransductionThymectomyTransplantation ChimeraConceptsCD8 T cellsCalcineurin/NFAT pathwayTolerance inductionCD8 toleranceT cell receptorCD4 cellsT cellsAllogeneic bone marrow transplantation modelNFAT pathwayT cell-intrinsic roleAnti-CD154 antibodyFailure of CD8Adoptive transfer studiesBone marrow transplantation modelBone marrow transplantationCell-intrinsic roleCalcineurin-NFAT pathwayCD8 cellsRegulatory cellsTransplantation toleranceMarrow transplantationTransplantation modelAnergy inductionNFAT1 deficiencyNuclear factor
2008
Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway
Haspot F, Fehr T, Gibbons C, Zhao G, Hogan T, Honjo T, Freeman GJ, Sykes M. Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway. Blood 2008, 112: 2149-2155. PMID: 18577709, PMCID: PMC2518911, DOI: 10.1182/blood-2007-12-127449.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenBone Marrow TransplantationCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleImmune ToleranceLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalPeptidesProgrammed Cell Death 1 ReceptorTransplantation, HomologousConceptsPD-1/PD-L1 pathwayPD-L1 pathwayBone marrow transplantationCD4 cellsCD8 cellsAlloreactive CD8PD-1Low-dose total body irradiationAlloreactive T cell populationsAllogeneic bone marrow transplantationAlloreactive CD8 cellsAnti-CD154 antibodyCD8 cell responsesTotal body irradiationCD4 T cellsLigand PD-L1T cell populationsRapid tolerizationCD4 helpDeath-1PD-L1Body irradiationMarrow transplantationActivation markersChronic infection