2025
Impact of memory T cells on SARS-CoV-2 vaccine response in hematopoietic stem cell transplant
VanOudenhove J, Liu Y, Nelakanti R, Kim D, Busarello E, Ovalle N, Qi Z, Mamillapalli P, Siddon A, Bai Z, Axtmayer A, Corso C, Kothari S, Foss F, Isufi I, Tebaldi T, Gowda L, Fan R, Seropian S, Halene S. Impact of memory T cells on SARS-CoV-2 vaccine response in hematopoietic stem cell transplant. PLOS ONE 2025, 20: e0320744. PMID: 40294012, PMCID: PMC12036906, DOI: 10.1371/journal.pone.0320744.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationMemory T cellsStem cell transplantationCell transplantationT cellsSARS-CoV-2Hematopoietic stem cell transplant recipientsAntigen-specific T-cell activationSARS-CoV-2 mRNA vaccinesSARS-CoV-2 vaccine responsesSevere diseaseAnti-spike IgGT cell activationAdaptive immune responsesRobust antibody responsesPost-vaccination responseSARS-CoV-2 infectionMRNA vaccine seriesSingle-cell RNAMyeloablative chemotherapyCellular responsesImmune profileVaccine responseCOVID-19 infectionMRNA vaccines
2024
Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation
Hanin A, Comi M, Sumida T, Hafler D. Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation. Life Science Alliance 2024, 7: e202402890. PMID: 39366761, PMCID: PMC11452476, DOI: 10.26508/lsa.202402890.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cellsEffector/memory cellsCentral nervous system milieuT cell environmentCD4 T cellsIFNG mRNA expressionCXCR3<sup>+</sup> cellsT cell homeostasisInhibition of SGK1Targeting lipid pathwaysMaintenance of immune surveillanceSerum/glucocorticoid-regulated kinaseImmune surveillanceHealthy donorsCytotoxic capacityEffector responsesInflammatory conditionsSGK1 activityMRNA expressionNervous systemSGK1Metabolic conditionsLipid pathwaysTissue adaptationReversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision
Abadie K, Clark E, Valanparambil R, Ukogu O, Yang W, Daza R, Ng K, Fathima J, Wang A, Lee J, Nasti T, Bhandoola A, Nourmohammad A, Ahmed R, Shendure J, Cao J, Kueh H. Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision. Immunity 2024, 57: 271-286.e13. PMID: 38301652, PMCID: PMC10922671, DOI: 10.1016/j.immuni.2023.12.006.Peer-Reviewed Original ResearchMeSH KeywordsCD8-Positive T-LymphocytesCell DifferentiationClone CellsEpigenesis, GeneticImmunologic MemoryMemory T CellsConceptsT cellsCD8<sup>+</sup> T cellsMemory T cell numbersT cell numbersOptimal immune responseImmune response magnitudeMemory potentialAcute infection modelResponse to stimulationImmune responseAntigen recognitionSelf-RenewalInfection modelPathogen clearanceMemory regulationCell numberEpigenetic silencingTCF1Response magnitudeCells
2023
Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice
Tyrrell D, Wragg K, Chen J, Wang H, Song J, Blin M, Bolding C, Vardaman D, Giles K, Tidwell H, Ali M, Janappareddi A, Wood S, Goldstein D. Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice. Nature Aging 2023, 3: 1576-1590. PMID: 37996758, PMCID: PMC11924142, DOI: 10.1038/s43587-023-00515-w.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAtherosclerosisCD8-Positive T-LymphocytesHumansMemory T CellsMiceMice, Inbred C57BLPlaque, AtheroscleroticConceptsT cellsMemory CD8Aged miceAtherosclerotic plaquesDepletion of CD8Effector memory subsetsStrong risk factorT cell activationEnhanced atherosclerosisSplenic CD8Adoptive transferDonor miceMemory subsetsRecipient miceRisk factorsCD8Therapeutic targetCell activationAtherosclerosisSingle-cell RNA sequencingMiceTranscriptomic signaturesAtherogenesisPlaquesRNA sequencingThe β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell functionToddler's T cells are taught in muco-school.
Khani-Habibabadi F, O'Connor K. Toddler's T cells are taught in muco-school. Science Immunology 2023, 8: eadj9555. PMID: 37540737, DOI: 10.1126/sciimmunol.adj9555.Peer-Reviewed Original ResearchIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensCD8-Positive T-LymphocytesHumansImmunologic MemoryLicensureMelanomaMemory T CellsMiceSignal TransductionConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive miceTissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15
Tieu R, Zeng Q, Zhao D, Zhang G, Feizi N, Manandhar P, Williams A, Popp B, Wood-Trageser M, Demetris A, Tso J, Johnson A, Kane L, Abou-Daya K, Shlomchik W, Oberbarnscheidt M, Lakkis F. Tissue-resident memory T cell maintenance during antigen persistence requires both cognate antigen and interleukin-15. Science Immunology 2023, 8: eadd8454. PMID: 37083450, PMCID: PMC10334460, DOI: 10.1126/sciimmunol.add8454.Peer-Reviewed Original ResearchConceptsAntigen persistenceIL-15Dendritic cellsT cellsAntigen presentationGraft-infiltrating dendritic cellsTissue-resident memory TCognate antigenAbsence of cognate antigenIL-15 transpresentationMemory T cell maintenanceT cell maintenanceChronic transplant rejectionKidney transplant modelIL-15 receptorAcute infection modelMemory TReceptor blockadeChronic rejectionTransplantation modelTransplant rejectionAcute infectionInterleukin-15Allograft pathologySterilizing immunityGOT1 regulates CD8+ effector and memory T cell generation
Xu W, Patel C, Zhao L, Sun I, Oh M, Sun I, Helms R, Wen J, Powell J. GOT1 regulates CD8+ effector and memory T cell generation. Cell Reports 2023, 42: 111987. PMID: 36640309, PMCID: PMC9943022, DOI: 10.1016/j.celrep.2022.111987.Peer-Reviewed Original ResearchMeSH KeywordsCD8-Positive T-LymphocytesCell DifferentiationGlucoseImmunologic MemoryMemory T CellsT-Lymphocytes, CytotoxicConceptsIntracellular redox balancePosttranslational regulationHIF proteinsMetabolic reprogrammingRedox balanceΑ-ketoglutarateGOT1T cell activationCell generationGenetic deletionEffector differentiationCritical roleCell activationDifferentiationRegulationProliferationReprogrammingBiosynthesisEffectorsProteinDeletionMechanisticallyCytotoxic functionFunctionPurine
2022
Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1.
Patel C, Heikamp E, Xu W, Sun I, Oh M, Sun I, Wen J, Tam A, Blosser R, Powell J. Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1. The Journal Of Immunology 2022, 209: 2287-2291. PMID: 36469844, PMCID: PMC10065985, DOI: 10.4049/jimmunol.2100669.Peer-Reviewed Original ResearchConceptsT cell differentiationT cellsMemory T cell differentiationMemory precursor phenotypeMemory T cellsEfficacy of vaccinesGlucocorticoid-regulated kinase 1Mechanistic targetRapamycin complex 2 (mTORC2) signalingT cell metabolismT cells resultsKinase 1Memory CD8Acute infectionGlucocorticoid kinase 1Tumor immunotherapyCD8Cell differentiationPrecursor phenotypeNuclear translocationPowerful targetSerumRecall capacityEssential regulatorCell metabolismUnadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses
Mao T, Israelow B, Peña-Hernández MA, Suberi A, Zhou L, Luyten S, Reschke M, Dong H, Homer RJ, Saltzman WM, Iwasaki A. Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science 2022, 378: eabo2523. PMID: 36302057, PMCID: PMC9798903, DOI: 10.1126/science.abo2523.Peer-Reviewed Original ResearchConceptsRespiratory mucosaSystemic immunityLethal SARS-CoV-2 infectionAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicSARS-CoV-2 infectionProtective mucosal immunityCross-reactive immunityT cell responsesCoronavirus 2 pandemicPrimary vaccinationParenteral vaccinesMucosal immunityVaccine strategiesRespiratory tractImmunoglobulin AMemory BImmune memoryPartial immunityCell responsesPoor immunityImmunitySpike proteinMucosaVaccineImmune landscape of human placental villi using single-cell analysis
Toothaker JM, Olaloye O, McCourt BT, McCourt CC, Silva TN, Case RM, Liu P, Yimlamai D, Tseng G, Konnikova L. Immune landscape of human placental villi using single-cell analysis. Development 2022, 149 PMID: 35050308, PMCID: PMC8935213, DOI: 10.1242/dev.200013.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticB-LymphocytesB7-H1 AntigenChorionic VilliFemaleFetusFlow CytometryHLA-DR AntigensHumansKiller Cells, NaturalLeukocyte Common AntigensLymphocyte ActivationMacrophagesMemory T CellsPlacentaPregnancyPregnancy Trimester, SecondReceptors, Cell SurfaceReceptors, ChemokineSingle-Cell AnalysisT-LymphocytesConceptsT cellsHuman placental villiPlacental villiImmune systemFetal immune systemMaternal immune systemFetal immune cellsAdult T-cellT cell receptor stimulationCell receptor stimulationHealthy pregnancyImmune landscapeMemory phenotypeImmune cellsFetal organsEnhanced proliferative capacityReceptor stimulationMultiple subtypesPV tissueComplex immune systemImaging modalitiesMass cytometryProliferative capacityMaternal mechanismsRecent reports
2021
Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy
Han J, Zhao Y, Shirai K, Molodtsov A, Kolling FW, Fisher JL, Zhang P, Yan S, Searles TG, Bader JM, Gui J, Cheng C, Ernstoff MS, Turk MJ, Angeles CV. Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy. Nature Cancer 2021, 2: 300-311. PMID: 34179824, PMCID: PMC8223731, DOI: 10.1038/s43018-021-00180-1.Peer-Reviewed Original ResearchMeSH KeywordsCD8-Positive T-LymphocytesHumansImmunologic FactorsImmunologic MemoryImmunotherapyMelanomaMemory T CellsConceptsT cell responsesMemory T cellsT cellsEffector memory T cellsResident memory T cellsMetastatic melanoma survivorsT cells persistStrong prognostic valueT cell receptorDurable responsesMemory CD8Melanoma patientsCancer survivorsPrognostic valueCancer immunotherapyMelanoma survivorsCells persistClonal repertoireSingle-cell RNA sequencingImmunotherapyTumorsExceptional responsePatient's skinClonotypesBloodResident memory T cells form during persistent antigen exposure leading to allograft rejection
Abou-Daya K, Tieu R, Zhao D, Rammal R, Sacirbegovic F, Williams A, Shlomchik W, Oberbarnscheidt M, Lakkis F. Resident memory T cells form during persistent antigen exposure leading to allograft rejection. Science Immunology 2021, 6 PMID: 33741656, PMCID: PMC8103522, DOI: 10.1126/sciimmunol.abc8122.Peer-Reviewed Original ResearchConceptsMemory T cellsEffector T cellsT cellsAllograft rejectionAntigen-SpecificTissue-resident memory T cellsFunctional memory T cellsResident memory T cellsMouse model of kidney transplantationGrafted T cellsPersistent antigen exposureModel of kidney transplantationRenal transplant outcomesRetransplantation experimentsDiscovery of therapeutic targetsExhaustion markersSurface phenotypeAntigen exposureInterferon-gTransplant outcomesKidney transplantationCognate antigenMouse modelOrgan transplantationTransplantation
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