2024
Exploring new perspectives in immunology
Medzhitov R, Iwasaki A. Exploring new perspectives in immunology. Cell 2024, 187: 2079-2094. PMID: 38670066, DOI: 10.1016/j.cell.2024.03.038.Peer-Reviewed Original Research
2023
IL-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 mice
2022
Unadjuvanted 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 proteinMucosaVaccine
2020
Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy.
Gopinath S, Lu P, Iwasaki A. Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy. The Journal Of Immunology 2020, 204: 1703-1707. PMID: 32122994, DOI: 10.4049/jimmunol.1900462.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsGenital herpes infectionMemory T cellsT cellsHerpes infectionVirus-specific effector T cellsVaginal applicationTopical vaginal applicationCD8 T cellsEffector T cellsProtective immune responseSingle topical applicationTopical aminoglycosidesGenital mucosaChemokine expressionVaccine strategiesImmune responseVaginal mucosaTopical applicationBarrier tissuesMiceRobust activationAminoglycoside antibioticsMucosaInfectionVEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas JL, Iwasaki A. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2020, 577: 689-694. PMID: 31942068, PMCID: PMC7100608, DOI: 10.1038/s41586-019-1912-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCD8-Positive T-LymphocytesCell Cycle CheckpointsCell Line, TumorCell MovementCentral Nervous SystemCross-PrimingFemaleGlioblastomaHEK293 CellsHumansImmunologic MemoryImmunologic SurveillanceLymph NodesLymphangiogenesisLymphatic VesselsMaleMelanomaMeningesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor CConceptsCD8 T cellsCentral nervous systemT cellsImmune responseBrain tumorsImmune surveillanceLymphatic drainageNervous systemAntigen-specific immune responsesDeep cervical lymph nodesCapacity of VEGFCervical lymph nodesCheckpoint blockade therapyMeningeal lymphatic systemVascular endothelial growth factor CNew therapeutic approachesUncontrolled tumor growthMeningeal lymphatic vasculatureBlockade therapyLymph nodesTherapeutic approachesMouse modelTumor growthMemory responsesTumors
2019
Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses
Jiang X, Muthusamy V, Fedorova O, Kong Y, Kim DJ, Bosenberg M, Pyle AM, Iwasaki A. Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses. Journal Of Experimental Medicine 2019, 216: 2854-2868. PMID: 31601678, PMCID: PMC6888973, DOI: 10.1084/jem.20190801.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Agents, ImmunologicalCD8-Positive T-LymphocytesDose-Response Relationship, DrugGene Expression ProfilingImmunologic MemoryInjections, IntralesionalMaleMelanoma, ExperimentalMiceOligoribonucleotidesProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceTumor BurdenConceptsAntitumor responseNucleic acid-sensing pathwaysSignificant tumor growth delayNumber of CD8Systemic antitumor responseRobust antitumor responseAnti-PD1 antibodyB16 tumor growthImmunogenic tumor modelsCytosolic nucleic acid-sensing pathwaysSingle-agent treatmentTumor growth delayTumor metastasis modelNK cellsMetastasis modelT lymphocytesImmune responseExtended survivalIntratumoral deliveryImmune memoryMyeloid cellsTumor growthGrowth delayTumor microenvironmentTumor modelEffector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection
Vesely M, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limón P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA. Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell 2019, 178: 1176-1188.e15. PMID: 31442406, PMCID: PMC7057720, DOI: 10.1016/j.cell.2019.07.032.Peer-Reviewed Original ResearchConceptsCD4 TTissue-resident memory T cellsBacterial infectionsResident memory T cellsFunction of airwayLife-long protectionEffector memory TMemory T cellsTh17 cellsTRM cellsΓδ TEffector cellsMemory TBacterial clearanceT cellsIL-7Adaptive immunityMouse modelMemory responsesVaccine designHost defenseLymphatic endothelial cellsDepletion studiesEndothelial cellsCellular originMigrant memory B cells secrete luminal antibody in the vagina
Oh JE, Iijima N, Song E, Lu P, Klein J, Jiang R, Kleinstein SH, Iwasaki A. Migrant memory B cells secrete luminal antibody in the vagina. Nature 2019, 571: 122-126. PMID: 31189952, PMCID: PMC6609483, DOI: 10.1038/s41586-019-1285-1.Peer-Reviewed Original ResearchConceptsMemory B cellsFemale reproductive tractB cellsPlasma cellsReproductive tractCD4 tissue-resident memory T cellsTissue-resident memory T cellsLower female reproductive tractHerpes simplex virus 2Genital herpes infectionMemory T cellsExpression of chemokinesSimplex virus 2CXCR3-dependent mannerLocal plasma cellsLuminal antibodyMucosal antibodiesHerpes infectionPrimary infectionMucosal barrierSecondary challengeVariety of pathogensT cellsLamina propriaInducible source
2016
CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2
Shin H, Kumamoto Y, Gopinath S, Iwasaki A. CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2. Nature Communications 2016, 7: 13346. PMID: 27827367, PMCID: PMC5105190, DOI: 10.1038/ncomms13346.Peer-Reviewed Original ResearchConceptsCD8 TRM cellsAntigen-presenting cellsGenital HSV-2 infectionTissue-resident memory CD8HSV-2 infectionTRM cellsDendritic cellsMemory CD8Protective immunityT cellsPopulations of APCsGenital HSV-2Protective immune responseFemale genital tractMHC class IHSV-2Genital tractAntigen presentationImmune responseLamina propriaViral infectionConfer protectionBarrier tissuesClass IInfectionExploiting Mucosal Immunity for Antiviral Vaccines
Iwasaki A. Exploiting Mucosal Immunity for Antiviral Vaccines. Annual Review Of Immunology 2016, 34: 575-608. PMID: 27168245, DOI: 10.1146/annurev-immunol-032414-112315.Peer-Reviewed Original ResearchConceptsMucosal immunityHuman immunodeficiency virusEffective immune protectionHost immune responseHerpes simplex virusImmunodeficiency virusMucosal vaccinesImmune protectionSuccessful vaccineImmune responseSimplex virusAntiviral vaccinesMucosal surfacesVaccine developmentVaccine designInfluenza virusFirst lineVaccineViral pathogensImmunityViral diseasesVirusDangerous pathogensPathogensDiseaseAccess of protective antiviral antibody to neuronal tissues requires CD4 T-cell help
Iijima N, Iwasaki A. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Nature 2016, 533: 552-556. PMID: 27225131, PMCID: PMC4883597, DOI: 10.1038/nature17979.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralBiological TransportBlood-Brain BarrierB-LymphocytesCapillary PermeabilityCD4-Positive T-LymphocytesDisease Models, AnimalFemaleGanglia, SpinalHerpes GenitalisHerpesvirus 2, HumanHistocompatibility Antigens Class IImmunologic MemoryIntegrin alpha4Interferon-gammaMiceNerve TissueNervous SystemNeuronsNoseReceptors, FcSpinal CordVesiculovirus
2015
Tissue instruction for migration and retention of TRM cells
Iijima N, Iwasaki A. Tissue instruction for migration and retention of TRM cells. Trends In Immunology 2015, 36: 556-564. PMID: 26282885, PMCID: PMC4567393, DOI: 10.1016/j.it.2015.07.002.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsMemory lymphocyte clustersTRM cellsT cellsCD4 tissue-resident memory T cellsRobust local immune responseCD8 TRM cellsEffector T cellsLocal immune responseMemory T cellsNon-lymphoid tissuesLymphocyte clustersImmune responseInfectious agentsIncoming pathogensCell homingRecent findingsCellsInfectionFindings
2014
A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells
Iijima N, Iwasaki A. A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells. Science 2014, 346: 93-98. PMID: 25170048, PMCID: PMC4254703, DOI: 10.1126/science.1257530.Peer-Reviewed Original ResearchConceptsMemory lymphocyte clustersMemory T cellsT cellsCD8 tissue-resident memory T cellsTissue-resident memory CD4 T cellsHerpes simplex virus 2 infectionTissue-resident memory T cellsSimplex virus 2 infectionMemory CD4 T cellsEfficient local controlPool of CD4Role of CD4CD4 T cellsVirus 2 infectionVaginal CD4Parabiotic miceGenital mucosaVaccine strategiesChemokine networkLymphocyte clustersHSV-2Viral infectionCD4Local controlInfection
2013
Tissue‐resident memory T cells
Shin H, Iwasaki A. Tissue‐resident memory T cells. Immunological Reviews 2013, 255: 165-181. PMID: 23947354, PMCID: PMC3748618, DOI: 10.1111/imr.12087.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementHumansImmunologic MemoryInflammationLymphocyte ActivationPhenotypeT-Lymphocyte SubsetsVaccinesVirus DiseasesVirusesConceptsMemory T cellsHuman immunodeficiency virusHerpes simplex virusGenital tractT cellsPeripheral tissuesImmune systemTissue-resident memory T cellsMemory T cell migrationTissue-resident memory cellsT cell-based vaccinesMemory T cell populationsMemory T cell subsetsAntibody-based vaccinesT cell recruitmentT cell subsetsNew vaccination strategiesT cell populationsSecondary lymphoid organsNon-lymphoid tissuesPortal of entryT cell migrationAdaptive immune systemTRM cellsEffector memory
2012
A vaccine strategy that protects against genital herpes by establishing local memory T cells
Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012, 491: 463-467. PMID: 23075848, PMCID: PMC3499630, DOI: 10.1038/nature11522.Peer-Reviewed Original Research
2009
Local advantage: skin DCs prime; skin memory T cells protect
Iwasaki A. Local advantage: skin DCs prime; skin memory T cells protect. Nature Immunology 2009, 10: 451-453. PMID: 19381136, PMCID: PMC3662044, DOI: 10.1038/ni0509-451.Peer-Reviewed Original ResearchMeSH KeywordsDendritic CellsHumansImmunologic MemoryLymphocyte ActivationSkinSkin Diseases, InfectiousT-Lymphocytes, Cytotoxic
2008
Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus
Iijima N, Linehan MM, Zamora M, Butkus D, Dunn R, Kehry MR, Laufer TM, Iwasaki A. Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. Journal Of Experimental Medicine 2008, 205: 3041-3052. PMID: 19047439, PMCID: PMC2605233, DOI: 10.1084/jem.20082039.Peer-Reviewed Original ResearchConceptsMemory Th1 cellsDendritic cellsTh1 cellsB cellsIFN-gammaHerpes simplex virus 2 infectionAntiviral protectionSimplex virus 2 infectionMemory CD4 T cellsFurther viral replicationTh1 memory responseHSV-2 infectionCD4 T cellsLocal dendritic cellsVirus 2 infectionAntigen-presenting cellsCytotoxic T lymphocytesMHC class IISite of infectionHerpes simplex virusTh1 responseImmunized miceRecall responsesViral antigensMHC class