2014
A Humanized Mouse Model of Autoimmune Insulitis
Milam A, Maher SE, Gibson JA, Lebastchi J, Wen L, Ruddle NH, Herold KC, Bothwell AL. A Humanized Mouse Model of Autoimmune Insulitis. Diabetes 2014, 63: 1712-1724. PMID: 24478396, PMCID: PMC3994947, DOI: 10.2337/db13-1141.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensCD4-Positive T-LymphocytesDiabetes Mellitus, Type 1Disease Models, AnimalHumansInsulin-Secreting CellsIslets of LangerhansMiceMice, Inbred NODT-Lymphocyte SubsetsConceptsT cellsDiabetic donorsInsulin stainingMouse modelAntigen-pulsed cellsAutoantigen-derived peptidesNOD mouse modelHumanized mouse modelType 1 diabetesPancreatic β-cellsT cell linesHuman T cellsIslet infiltrationAutoimmune diabetesNOD-SCIDAutoimmune insulitisHuman diabetesDestructive infiltrationMouse isletsMechanism of inductionΒ-cellsDiabetesDiabetes researchDisease modelsInsulitisPillars article: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994. 264: 703-707.
De Togni P, Goellner J, Ruddle NH, Streeter PR, Andrea F, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J, Russell JH, Karr R, Chaplin DD. Pillars article: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994. 264: 703-707. The Journal Of Immunology 2014, 192: 2010-4. PMID: 24563504.Peer-Reviewed Original Research
2011
Blocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses
Motallebzadeh R, Rehakova S, Conlon TM, Win TS, Callaghan CJ, Goddard M, Bolton EM, Ruddle NH, Bradley JA, Pettigrew GJ. Blocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses. The FASEB Journal 2011, 26: 51-62. PMID: 21926237, DOI: 10.1096/fj.11-186973.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBone MarrowCD4-Positive T-LymphocytesChoristomaChronic DiseaseGraft RejectionHeart TransplantationIsoantibodiesLymphoid TissueLymphotoxin beta ReceptorLymphotoxin-betaMiceMice, Inbred C57BLMice, KnockoutMyocardiumNeovascularization, PathologicRecombinant Fusion ProteinsSignal TransductionSpleenTransplantation, HomologousConceptsTertiary lymphoid organsCardiac allograftsHeart allograftsB cellsLymphotoxin β receptor (LTβR) signalingEctopic lymphoid tissueGerminal center activityLTβR-IgTLO formationPostoperative administrationAccelerated rejectionHumoral autoimmunityAlloimmune responseAutoantibody productionAutoantibody responseHumoral responseLymphoid organsLymphoid tissueLymphoid organogenesisEffector antibodiesMouse modelAllograftsTransplantationAutoantibodiesCells
2010
Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs
Penaranda C, Tang Q, Ruddle NH, Bluestone JA. Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs. Diabetes 2010, 59: 1461-1468. PMID: 20299465, PMCID: PMC2874707, DOI: 10.2337/db09-1129.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsPancreatic lymph nodesNOD miceLymph nodesDiabetes developmentDiabetic miceLymphoid organsSpontaneous type 1 diabetesB cell compartmentalizationExit of lymphocytesNonobese diabetic (NOD) miceAge-matched miceDevelopment of diabetesPrevention of diabetesNaive T cellsType 1 diabetesB cell compartmentWeeks of ageSignificant insulitisIslet destructionTreatment withdrawalAutoimmune destructionClinical scoresAccelerated diseaseDisease progression
2009
Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens
Akirav EM, Bergman CM, Hill M, Ruddle NH. Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens. Journal Of Neuroscience Research 2009, 87: 3511-3519. PMID: 19125411, PMCID: PMC4429897, DOI: 10.1002/jnr.21981.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAutoantigensAutoimmunityBiomarkersCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCentral Nervous SystemChemotaxis, LeukocyteDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleInterferon-gammaInterleukin-10Interleukin-17Interleukin-2 Receptor alpha SubunitLymphocyte ActivationMiceMice, Inbred C57BLMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRatsT-Lymphocytes, RegulatoryConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinAutoimmune encephalomyelitisT cellsIL-10-producing cellsRegulatory T cellsTissue-restricted antigensCentral nervous systemField of autoimmunityT cell activationTreg depletionEAE severitySelf antigensOligodendrocyte glycoproteinForeign antigensExperimental diseaseNervous systemRelated antigensMiceSelf-antigen specificityAntigenTregsEncephalomyelitisAutoimmunityRats
2006
Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid
Marinkovic T, Garin A, Yokota Y, Fu YX, Ruddle NH, Furtado GC, Lira SA. Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. Journal Of Clinical Investigation 2006, 116: 2622-2632. PMID: 16998590, PMCID: PMC1570377, DOI: 10.1172/jci28993.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesCell Adhesion MoleculesCell CommunicationCell MovementChemokine CCL21ChemokinesChemokines, CCDendritic CellsDNA-Binding ProteinsGene ExpressionGreen Fluorescent ProteinsInhibitor of Differentiation Protein 2Lymphoid TissueLymphotoxin-alphaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, CCR7Receptors, ChemokineThyroid DiseasesThyroid Gland
2004
MAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection
Soderberg KA, Linehan MM, Ruddle NH, Iwasaki A. MAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection. The Journal Of Immunology 2004, 173: 1908-1913. PMID: 15265924, DOI: 10.4049/jimmunol.173.3.1908.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralCD4-Positive T-LymphocytesCell Adhesion MoleculesDendritic CellsFemaleHerpes GenitalisHerpesvirus 2, HumanImmunoglobulin GImmunoglobulinsLymph NodesLymphocyte ActivationLymphotoxin-alphaLymphotoxin-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMucoproteinsSacrococcygeal RegionSplenectomyT-Cell Antigen Receptor SpecificityTh1 CellsVaginitisConceptsBeta-deficient miceSacral lymph nodesLymph nodesMesenteric lymph nodesWild-type miceGenital mucosaHerpes simplex virus 2 infectionIntravaginal HSV-2 infectionLT alpha-deficient miceMucosal addressin cell adhesion molecule-1Simplex virus 2 infectionCell adhesion molecule-1Mucosal lymph nodesAlpha-deficient miceCervical lymph nodesHSV-2 infectionVirus 2 infectionHSV type 2Potent immune responsesAdhesion molecule-1Intravaginal infectionTh1 responseDendritic cellsIgG responsesIliac artery
2002
Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ
Constant SL, Brogdon JL, Piggott DA, Herrick CA, Visintin I, Ruddle NH, Bottomly K. Resident lung antigen-presenting cells have the capacity to promote Th2 T cell differentiation in situ. Journal Of Clinical Investigation 2002, 110: 1441-1448. PMID: 12438442, PMCID: PMC151814, DOI: 10.1172/jci16109.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsAntigen PresentationAntigen-Presenting CellsAntigens, ProtozoanCD4-Positive T-LymphocytesCell DifferentiationCell MovementCytokinesInterleukin-10Interleukin-6Leishmania majorLungLymph NodesLymphotoxin-alphaMiceMice, Inbred C57BLMice, KnockoutTh1 CellsTh2 CellsConceptsAntigen-presenting cellsTh2 T cell differentiationT cell primingT cell differentiationCell primingAntigen-loaded antigen-presenting cellsLung antigen-presenting cellsPulmonary antigen-presenting cellsResident antigen-presenting cellsPreferential primingAntigen-specific T cellsSecondary lymphoid organsTh2-dominated responsesTh1 responseAntigen exposureIL-10Th2 typeAntigen uptakeIL-6Lung microenvironmentLymphoid organsTh2 cellsIntranasal deliveryLung tissueAirway epitheliumRole of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection
Suresh M, Lanier G, Large MK, Whitmire JK, Altman JD, Ruddle NH, Ahmed R. Role of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection. Journal Of Virology 2002, 76: 3943-3951. PMID: 11907234, PMCID: PMC136110, DOI: 10.1128/jvi.76.8.3943-3951.2002.Peer-Reviewed Original ResearchConceptsT cell responsesCD8 T cellsLymphocytic choriomeningitis virusT cellsT cell activationLymphoid architectureMajor histocompatibility complex class I tetramersVirus-specific CD8 T cell responsesLCMV-specific CD8 T cellsLCMV-specific T-cell responsesVirus-specific CD8 T cellsAntigen-specific T cell responsesCD8 T cell responsesLCMV-specific T cellsT cell-mediated immunopathologyLTalpha-deficient miceClass I tetramersAcute viral infectionCD4 T cellsAdoptive transfer experimentsCell transfer experimentsLCMV clearanceNonlymphoid organsAdoptive transferAcute infection
1997
Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection.
Soong L, Chang CH, Sun J, Longley BJ, Ruddle NH, Flavell RA, McMahon-Pratt D. Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection. The Journal Of Immunology 1997, 158: 5374-83. PMID: 9164958, DOI: 10.4049/jimmunol.158.11.5374.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesDNA-Binding ProteinsHistocompatibility Antigens Class IIImmunity, CellularLeishmaniaLeishmaniasisMiceMice, Inbred C57BLProteinsConceptsII-/- miceLeishmania amazonensis infectionRag2-/- miceT cellsAmazonensis infectionMHC classL. amazonensis-infected miceWild-type C57BL/6 miceLarge ulcerating lesionsMonocytes/granulocytesRole of CD4Course of infectionMonocytes/macrophagesStrains of miceMHC class IWild-type CD4T cell developmentUlcerating lesionFunctional CD4Lymphocyte subsetsC57BL/6 miceTh1 cellsInflammatory responseLesion pathologyImmune response
1996
Leishmania‐infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells
Kima P, Soong L, Chicharro C, Ruddle N, McMahon‐Pratt D. Leishmania‐infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells. European Journal Of Immunology 1996, 26: 3163-3169. PMID: 8977318, DOI: 10.1002/eji.1830261249.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigens, ProtozoanCD4-Positive T-LymphocytesFemaleLeishmaniaLeishmania majorLeishmania mexicanaMacrophagesMiceMice, Inbred CBAConceptsT cellsAntigen presentationParasite antigensMajor histocompatibility complex (MHC) class II moleculesMHC class II pathwayActivation of CD4Peritoneal exudate cellsClass II pathwayClass II moleculesHost immune systemCell linesT cell linesAmastigote antigensLeishmania antigenAntigen sequestrationLeishmania amastigotesMacrophage cell lineExudate cellsCD4Immune systemLive parasitesParasite moleculesAntigenMacrophagesInfected cells