2024
Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Wu M, Valenca-Pereira F, Cendali F, Giddings E, Pham-Danis C, Yarnell M, Novak A, Brunetti T, Thompson S, Henao-Mejia J, Flavell R, D’Alessandro A, Kohler M, Rincon M. Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies. Nature Communications 2024, 15: 4444. PMID: 38789421, PMCID: PMC11126743, DOI: 10.1038/s41467-024-48653-y.Peer-Reviewed Original ResearchConceptsMethylation-controlled J proteinCAR-T cellsEfficacy of adoptive T cell therapyCD8+ CAR T cellsAdoptive T cell therapyT-cell therapyCD8 cellsT cellsOvalbumin (OVA)-specific CD8T cell adoptive therapyCD8+ T cellsMelanoma tumors in vivoFunction of T cellsAdoptive cellular therapyMurine B-cell leukemiaPromote T cell functionB-cell leukemiaT cell functionTumors in vivoPre-clinical studiesAnti-tumor activityIn vivo efficacyAdoptive therapyPotential therapeutic strategyEndogenous negative regulator
2020
Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
Silasi M, You Y, Simpson S, Kaislasuo J, Pal L, Guller S, Peng G, Ramhorst R, Grasso E, Etemad S, Durosier S, Aldo P, Mor G. Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua. Scientific Reports 2020, 10: 5785. PMID: 32238853, PMCID: PMC7113245, DOI: 10.1038/s41598-020-62593-9.Peer-Reviewed Original ResearchConceptsHuman chorionic gonadotropinCXCL10 expressionChorionic gonadotropinPotent immune-modulatory effectsImmune system undergoesImmune modulatory effectsEndometrial stromal cellsImmune cell recruitmentMaternal-fetal interfaceImmune regulatory functionsProcess of implantationCD8 cellsCytokine profilePregnancy progressesFetal interfaceDecidual samplesImmune populationsImmune factorsHuman deciduaT cellsDecidual cellsCell recruitmentModulatory effectsEarly hormoneStromal cellsShort-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade
Ajona D, Ortiz-Espinosa S, Lozano T, Exposito F, Calvo A, Valencia K, Redrado M, Remírez A, Lecanda F, Alignani D, Lasarte J, Macaya I, Senent Y, Bértolo C, Sainz C, Gil-Bazo I, Eguren-Santamaría I, Lopez-Picazo J, Gonzalez A, Perez-Gracia J, de Andrea C, Vicent S, Sanmamed M, Montuenga L, Pio R. Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade. Nature Cancer 2020, 1: 75-85. PMID: 35121837, DOI: 10.1038/s43018-019-0007-9.Peer-Reviewed Original ResearchConceptsPD-1 blockadeCell death protein 1 (PD-1) pathwayPD-1 immune checkpoint blockadeCD8/Treg ratioHigh IGF-1R expressionInsulin-like growth factor-1Cell lung cancer treatmentIGF-1 levelsPD-1 inhibitionImmune checkpoint blockadeTumor-specific immunityCell lung cancerIGF-1R expressionHigher plasma levelsLung cancer progressionLung cancer treatmentIGF-1 receptorGrowth factor-1Protein 1 pathwayTreg ratioCD8 cellsCheckpoint blockadePD-1Syngeneic modelLung cancer
2019
In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease
Morin-Zorman S, Wysocki C, Zhu J, Li H, Zorman S, Matte-Martone C, Kisanga E, McNiff J, Jain D, Gonzalez D, Rothstein DM, Lakkis FG, Haberman A, Shlomchik WD. In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease. Blood Advances 2019, 3: 2082-2092. PMID: 31296496, PMCID: PMC6650737, DOI: 10.1182/bloodadvances.2019000227.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCD11c AntigenCell CommunicationDendritic CellsDisease Models, AnimalFluorescent Antibody TechniqueGene ExpressionGenes, ReporterGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHistocompatibility Antigens Class IImmunophenotypingLymphocyte DepletionMiceMice, TransgenicProtein BindingReceptors, Antigen, T-CellSkin DiseasesT-Lymphocyte SubsetsT-LymphocytesTransplantation, HomologousConceptsDonor dendritic cellsCD8 cellsT cellsGVHD lesionsHost diseaseCD4 cellsDendritic cellsAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationMajority of CD4Dynamics of CD4Stem cell transplantationCutaneous graftAntibody infusionCell transplantationMyeloid cellsIntravital microscopyAcute deletionMajor causeLesionsTarget tissuesCD103CD4InfusionMHCIIMultiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry
Carvajal-Hausdorf DE, Patsenker J, Stanton KP, Villarroel-Espindola F, Esch A, Montgomery RR, Psyrri A, Kalogeras KT, Kotoula V, Foutzilas G, Schalper KA, Kluger Y, Rimm DL. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry. Clinical Cancer Research 2019, 25: 3054-3062. PMID: 30796036, PMCID: PMC6522272, DOI: 10.1158/1078-0432.ccr-18-2599.Peer-Reviewed Original ResearchConceptsTrastuzumab-treated patientsT cell infiltrationCD8 T cell infiltrationCohort of patientsCytotoxic T cellsMass cytometryCase-control seriesExtracellular domainMechanism of actionTrastuzumab benefitAdjuvant treatmentCD8 cellsRecurrence eventsT cellsAntibody panelImmune systemPatientsMetal-conjugated antibodiesQuantitative immunofluorescenceTrastuzumabImaging Mass CytometryHER2Signaling targetsObjective measurementsCytometry
2017
Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response
Jayakumar A, Bothwell ALM. Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response. Neoplasia 2017, 19: 595-605. PMID: 28654863, PMCID: PMC5487300, DOI: 10.1016/j.neo.2017.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis ColiAnimalsBecaplerminBiomarkersCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Transformation, NeoplasticCytotoxicity, ImmunologicDisease Models, AnimalDisease ProgressionGene DeletionGene ExpressionInterleukin-4Intestinal MucosaIntestine, SmallMiceMice, KnockoutMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-sisSTAT6 Transcription FactorConceptsIntestinal tumorigenesisIL-4-induced STAT6Tumor-promoting growth factorsAntitumor T-cell responsesHuman colorectal cancer tissuesMore CD8 cellsPD-1 expressionEpithelial cellsExpansion of MDSCsT cell responsesIL-4 expressionCell proliferationColorectal cancer tissuesPlatelet-derived growth factor-BBIntestinal tumor progressionIntestinal epithelial cellsGrowth factor-BBColon cancer cell linesCD8 responsesPolyp progressionStrong CD8Cancer cell linesCD4 cellsCD8 cellsImmunosuppressive mediators
2015
Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?
Elder RW, George RP, McCabe NM, Rodriguez III FH, Book WM, Mahle WT, Kirk AD. Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter? Pediatric Cardiology 2015, 36: 1411-1416. PMID: 25916315, PMCID: PMC5319831, DOI: 10.1007/s00246-015-1174-9.Peer-Reviewed Original ResearchConceptsAdult congenital heart diseaseCongenital heart diseaseACHD patientsHeart diseaseExact testMean percentageImmune phenotypic changesT lymphocyte compositionCD8 T cellsFisher's exact testPolychromatic flow cytometryT cell maturationMann-Whitney ULower mean percentageImmune exhaustionImmunologic exhaustionPrior sternotomyCD8 lymphocytesCD4 cellsCD8 cellsLymphocyte compositionMedian ageClinical impactT cellsT lymphocytes
2013
A General Approach for Controlling Transcription and Probing Epigenetic Mechanisms: Application to the Cd4 Locus
Wan M, Kaundal R, Huang H, Zhao J, Yang X, Chaiyachati BH, Li S, Chi T. A General Approach for Controlling Transcription and Probing Epigenetic Mechanisms: Application to the Cd4 Locus. The Journal Of Immunology 2013, 190: 737-747. PMID: 23293358, PMCID: PMC3744393, DOI: 10.4049/jimmunol.1201278.Peer-Reviewed Original Research
2010
STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5
Cetica V, Santoro A, Gilmour K, Sieni E, Beutel K, Pende D, Marcenaro S, Koch F, Grieve S, Wheeler R, Zhao F, Stadt U, Griffiths G, Aricò M. STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis type 5. Journal Of Medical Genetics 2010, 47: 595. PMID: 20798128, PMCID: PMC4115259, DOI: 10.1136/jmg.2009.075341.Peer-Reviewed Original ResearchConceptsFamilial haemophagocytic lymphohistiocytosisSTXBP2 mutationsDisease related genesHaematopoietic stem cell transplantationStem cell transplantationRare immune deficiencyScreening of familiesMunc13-4Nucleotide changesSyntaxin-11Genetic heterogeneitySTX11 genesCD8 cellsHaemophagocytic lymphohistiocytosisCell transplantationClinical courseImmune deficiencyRelated genesFunctional studiesCell cytotoxicityFHL-5MutationsUncontrolled inflammationGenetic defectsGenetic mutations
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 factorMemory CD8. + T Cells Specific for Minor Histocompatibility Antigen H60 Can Mediate the Graft-Versus-Leukemia Effect.
Li N, Matte-Martone C, Venkatesan S, Shlomchik W. Memory CD8. + T Cells Specific for Minor Histocompatibility Antigen H60 Can Mediate the Graft-Versus-Leukemia Effect. Blood 2009, 114: 1332. DOI: 10.1182/blood.v114.22.1332.1332.Peer-Reviewed Original ResearchMemory T cellsCD8 cellsT cellsLess GVHDCP-CMLImmune reconstitutionVaccinated miceMouse modelAntigen distributionAllogeneic hematopoietic stem cell transplantationBC-CMLCentral memory T cellsStrong anti-tumor responsesHematopoietic stem cell transplantationHuman memory T cellsRecipient B6 miceDonor T cellsAnti-tumor responseCentral memory phenotypeStem cell transplantationMemory CD8 cellsNaïve T cellsT Cells SpecificChronic myelogenous leukemiaGraft-VersusCD40L-specific mAb mediates its tolerogenic effects through engagement of FcgRIIB, not via depletion of activated T cells (141.17)
Lucas C, Fehr T, Haspot F, Sykes M. CD40L-specific mAb mediates its tolerogenic effects through engagement of FcgRIIB, not via depletion of activated T cells (141.17). The Journal Of Immunology 2009, 182: 141.17-141.17. DOI: 10.4049/jimmunol.182.supp.141.17.Peer-Reviewed Original ResearchCD8 T cellsBone marrow cellsAllogeneic bone marrow cellsT cellsCD8 cellsCD8 T cell toleranceLong-term mixed chimerismPeripheral CD8 T cellsTotal body irradiationDepletion of activated T cellsRecipient B cellsT cell toleranceFc-dependent functionsCD40L mAbDonor BMMixed chimerismDonor leukocytesBody irradiationKO recipientsB6 miceTolerogenic effectGraft acceptanceMarrow cellsFcgRIIbCD8
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
2005
CD8+ but Not CD4+ T Cells Require Cognate Interactions with Target Tissues To Mediate GVHD across Only Minor H Antigens but CD4+ and CD8+ T Cells Both Require Direct Leukemic Contact for GVL.
Shlomchik W, Matte C, Liu J, Jain D, McNiff J. CD8+ but Not CD4+ T Cells Require Cognate Interactions with Target Tissues To Mediate GVHD across Only Minor H Antigens but CD4+ and CD8+ T Cells Both Require Direct Leukemic Contact for GVL. Blood 2005, 106: 580. DOI: 10.1182/blood.v106.11.580.580.Peer-Reviewed Original ResearchCD8-mediated GVHDDirect cognate interactionT cellsSecond transplantCD4 cellsCD8 cellsHost antigensCognate interactionMHCII expressionBone marrowDonor CD4 cellsDonor-derived APCsTarget tissuesT-cell releaseAlloreactive T cellsBone marrow chimerasMinor H antigensCognate T cellsChimeric recipientsDonor BMGVHD lethalityHistologic GVHDHost APCsLess GVHDLeukemic expressionCD8+ Central Memory T Cells Mediate Graft-Versus-Host Disease Although Retain Graft-Versus-Leukemia Effect.
Zheng H, Matte C, Anderson B, Venkatesan S, Jain D, Shlomchik M, Shlomchik W. CD8+ Central Memory T Cells Mediate Graft-Versus-Host Disease Although Retain Graft-Versus-Leukemia Effect. Blood 2005, 106: 1312. DOI: 10.1182/blood.v106.11.1312.1312.Peer-Reviewed Original ResearchCD8 cellsMemory T cellsMore weight lossCell recipientsT cellsCM cellsWeight lossGraft-VersusHistologic GVHDLess weight lossEffector functionsBALB/c recipientsEffector memory T cellsCentral memory T cellsDay 16Central memory TClear histologic evidencePeriportal inflammatory infiltrationReconstitution of immunityDonor T cellsTime pointsMost time pointsDonor BMEarly time pointsEffective GVL
2004
Donor APCs are required for maximal GVHD but not for GVL
Matte CC, Liu J, Cormier J, Anderson BE, Athanasiadis I, Jain D, McNiff J, Shlomchik WD. Donor APCs are required for maximal GVHD but not for GVL. Nature Medicine 2004, 10: 987-992. PMID: 15286785, DOI: 10.1038/nm1089.Peer-Reviewed Original ResearchConceptsDonor antigen-presenting cellsAntigen-presenting cellsCD8 cellsMouse modelDonor major histocompatibility complex (MHC) class IBone marrowDonor-derived antigen-presenting cellsChronic phase chronic myelogenous leukemiaHematopoietic antigen-presenting cellsRecipient antigen-presenting cellsHost antigen-presenting cellsMajor histocompatibility complex class IAlloreactive CD8 cellsRecipients of MHCHistocompatibility complex class IDonor-derived cellsMinor histocompatibility antigensChronic myelogenous leukemiaDeficient bone marrowComplex class IHost diseaseGVHDHistocompatibility antigensMyelogenous leukemiaInitial primingIncreasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model
Friedman J, Alpdogan O, van den Brink M, Liu C, Hurwitz D, Boyd A, Kupper T, Burakoff S. Increasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model. Transplantation And Cellular Therapy 2004, 10: 448-460. PMID: 15205666, DOI: 10.1016/j.bbmt.2004.03.005.Peer-Reviewed Original ResearchConceptsOld T cellsT cellsSurface antigen expressionCD8 cellsAntigen expressionEffector activityT cell receptor repertoireBone marrow transplant modelCD4 T cell expansionT-cell doseSeverity of GVHDType 1 cytokinesT cell expansionAntigen-driven proliferationT-cell groupAdult T-cellT-cell ageSuccinimidyl ester labelingYoung T cellsAge-dependent declineLethal GVHDHost diseasePathologic evidenceTransplant modelCytolytic function
2003
Immunobiologic analysis of arterial tissue in Buerger's disease
Lee T, Seo J, Sumpio BE, Kim SJ. Immunobiologic analysis of arterial tissue in Buerger's disease. European Journal Of Vascular And Endovascular Surgery 2003, 25: 451-457. PMID: 12713785, DOI: 10.1053/ejvs.2002.1869.Peer-Reviewed Original ResearchConceptsThromboangiitis obliteransT cellsVaso vasorumI-NOSVCAM-1Endothelial cellsDegree of recanalizationT lymphocyte infiltrationCD4 T cellsInflammatory cytokine detectionInterferon-gamma mRNABuerger's diseasePatent arteriesCD8 cellsImmunologic injuryLymphocyte infiltrationImmune inflammationImmune injuryLuminal obliterationEtiologic mechanismsTUNEL studiesCell activationArterial wallRT-PCRCytokine detection
1999
Peripheral blood mononuclear cell markers in antiretroviral therapy-naive HIV-infected and high risk seronegative adolescents
Douglas S, Rudy B, Muenz L, Moscicki A, Wilson C, Holland C, Crowley-Nowick P, Vermund S. Peripheral blood mononuclear cell markers in antiretroviral therapy-naive HIV-infected and high risk seronegative adolescents. AIDS 1999, 13: 1629-1635. PMID: 10509563, DOI: 10.1097/00002030-199909100-00005.Peer-Reviewed Original ResearchConceptsAdolescent Medicine HIV/AIDS Research NetworkHIV-negative adolescentsHIV-negative femalesHIV-positive femalesHIV-positive adolescentsAntiretroviral therapyHIV infectionHealthy adolescentsAntiretroviral therapy-naive HIVTotal CD4 cell countsThree-color flow cytometryMononuclear cell markersNaive CD8 cellsTherapy-naive HIVCD4 cell countHIV-negative subjectsHIV-positive malesAIDS Research NetworkHigh-risk HIVCD8 memory cellsNatural killer cellsTotal leukocyte countREACH cohortSeronegative adolescentsCD8 cells
1998
Tumor‐specific peptides in cutaneous T‐cell lymphoma: Association with class I major histocompatibility complex and possible derivation from the clonotypic T‐cell receptor
Berger C, Longley B, Imaeda S, Christensen I, Heald P, Edelson R. Tumor‐specific peptides in cutaneous T‐cell lymphoma: Association with class I major histocompatibility complex and possible derivation from the clonotypic T‐cell receptor. International Journal Of Cancer 1998, 76: 304-311. PMID: 9579563, DOI: 10.1002/(sici)1097-0215(19980504)76:3<304::aid-ijc3>3.0.co;2-z.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, NeoplasmCD8-Positive T-LymphocytesGenes, T-Cell Receptor betaHistocompatibility Antigens Class IHumansLymphoma, T-Cell, CutaneousMolecular Sequence DataPeptidesProtein ConformationSequence AlignmentSequence Homology, Amino AcidSkin NeoplasmsT-Lymphocyte SubsetsT-Lymphocytes, CytotoxicTumor Necrosis Factor-alphaConceptsCutaneous T-cell lymphomaT cell receptorClonotypic T cell receptorIdiotypic peptideT-cell lymphomaCD8 cellsClass I moleculesCTCL patientsClass I peptidesTumor cellsClass II moleculesAnti-tumor vaccinesClass I major histocompatibilityMalignant T cellsCTCL tumor cellsTumor-specific peptidesI peptidesTNF-alpha assayCD8 responsesNovel class IPeptide-binding motifTumor necrosisT cellsCTCL cells
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