2022
A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells
Axisa P, Yoshida T, Lucca L, Kasler H, Lincoln M, Pham G, Del Priore D, Carpier J, Lucas C, Verdin E, Sumida T, Hafler D. A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells. Science Translational Medicine 2022, 14: eabl3651. PMID: 36516268, DOI: 10.1126/scitranslmed.abl3651.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesDisease Models, AnimalGenome-Wide Association StudyHistone DeacetylasesHumansMiceMultiple SclerosisT-Lymphocytes, RegulatoryConceptsExperimental autoimmune encephalitisRegulatory T cellsHistone deacetylase 7Multiple sclerosisT cellsMouse modelFunction of Foxp3CD4 T cellsHigher suppressive capacityVivo modelingAutoimmune encephalitisEAE severityImmunosuppressive subsetAutoimmune diseasesImmunomodulatory roleSuppressive capacityImmune cellsDisease onsetDistinct molecular classesSusceptibility lociGenetic susceptibility lociSingle-cell RNA sequencingDisease riskPatient samplesProtective variants
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