2022
Obesity aggravates contact hypersensitivity reaction in mice
Majewska‐Szczepanik M, Kowalczyk P, Marcińska K, Strzępa A, Lis GJ, Wong FS, Szczepanik M, Wen L. Obesity aggravates contact hypersensitivity reaction in mice. Contact Dermatitis 2022, 87: 28-39. PMID: 35234303, PMCID: PMC9949724, DOI: 10.1111/cod.14088.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesDermatitis, Allergic ContactHumansInflammationInterleukin-17MiceMice, Inbred C57BLMice, KnockoutObesityConceptsContact hypersensitivityFecal microbiota transplantationQuantitative polymerase chain reactionIL-17AObese miceEnhanced contact hypersensitivityGut microbiota dysbiosisLow-grade inflammationContact hypersensitivity reactionInfluence of obesityInflammatory skin diseaseT helper 1Antigen-specific responsesHigh-fat dietSubcutaneous adipose tissueProinflammatory CD4Proinflammatory milieuCytokine profileMicrobiota dysbiosisDendritic cellsLymph nodesMicrobiota transplantationHelper 1Hypersensitivity reactionsImmune cells
2020
Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice
Pearson JA, Li Y, Majewska-Szczepanik M, Guo J, Zhang L, Liu Y, Wong FS, Wen L. Insulin-Reactive T Cells Convert Diabetogenic Insulin-Reactive VH125 B Cells Into Tolerogenic Cells by Reducing Germinal Center T:B Cell Interactions in NOD Mice. Frontiers In Immunology 2020, 11: 585886. PMID: 33262765, PMCID: PMC7688534, DOI: 10.3389/fimmu.2020.585886.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantigensB-LymphocytesCD4-Positive T-LymphocytesCell CommunicationDiabetes Mellitus, Type 1Germinal CenterImmune ToleranceInsulinMiceMice, Inbred NODMice, TransgenicConceptsB cell interactionsTransgenic NOD miceNOD miceT cellsB cellsT1D developmentAntigen-specific regulatory T cellsInsulin-reactive B cellsInsulin-reactive T cellsNon-obese diabetic (NOD) miceGerminal center TInsulin-reactive CD4Non-germinal centerCell interactionsCostimulatory molecule expressionRegulatory T cellsType 1 diabetesGC B cellsTolerogenic cellsAdoptive transferDiabetic miceTGFβ secretionMolecule expressionIgG isotypeKey autoantigen
2014
IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice
Tan Q, Majewska-Szczepanik M, Zhang X, Szczepanik M, Zhou Z, Wong FS, Wen L. IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice. Diabetes 2014, 63: 2761-2775. PMID: 24696448, PMCID: PMC4113073, DOI: 10.2337/db13-1504.Peer-Reviewed Original ResearchConceptsDiabetogenic T cellsNOD miceRapid progressionT cellsInterleukin-1 receptor-associated kinase MOrgan-specific autoimmune diseasesType 1 diabetes mellitusAnti-insulin autoantibodiesImmunodeficient NOD miceImpaired glucose toleranceAntigen-presenting functionNonobese diabetic (NOD) miceToll-like receptor pathwayAntigen-presenting cellsEnhanced activationType 1 diabetesInnate immune pathwaysIRAK-M deficiencyInnate immune processesInsulin-secreting pancreatic β-cellsPancreatic β-cellsSevere insulitisAutoimmune diabetesDendritic cellsDiabetes mellitusEpicutaneous Immunization with TNP-Ig and Zymosan Induces TCRαβ+ CD4+ Contrasuppressor Cells That Reverse Skin-Induced Suppression via IL-17A
Majewska-Szczepanik M, Strzepa A, Marcińska K, Wen L, Szczepanik M. Epicutaneous Immunization with TNP-Ig and Zymosan Induces TCRαβ+ CD4+ Contrasuppressor Cells That Reverse Skin-Induced Suppression via IL-17A. International Archives Of Allergy And Immunology 2014, 164: 122-136. PMID: 24993442, PMCID: PMC4141016, DOI: 10.1159/000363446.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, CutaneousAnimalsAntigensCD4-Positive T-LymphocytesDermatitis, ContactHaptensImmunity, InnateImmunizationImmunoglobulinsImmunosuppression TherapyInterleukin-17Lymph NodesMiceMice, Inbred C57BLMice, Inbred CBAMyeloid Differentiation Factor 88Receptors, Antigen, T-Cell, alpha-betaSkinToll-Like Receptor 2Transforming Growth Factor betaTrinitrobenzenesVaccinationZymosanConceptsSkin-induced suppressionSuppression of CHSContact hypersensitivityEC immunizationEpicutaneous immunizationTNP-IgAdoptive cell transfer experimentsProtein antigensT contrasuppressor cellsT suppressor cellsLymph node cellsCell transfer experimentsCHS responseContrasuppressor cellsIL-17ASuppressor cellsCytokine productionNode cellsImmunogenic antigensPresence of zymosanAntigen E.ImmunizationInnate immunityCD4Gauze patches
2013
Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes
Hu C, Ding H, Zhang X, Wong FS, Wen L. Combination Treatment With Anti-CD20 and Oral Anti-CD3 Prevents and Reverses Autoimmune Diabetes. Diabetes 2013, 62: 2849-2858. PMID: 23447122, PMCID: PMC3717853, DOI: 10.2337/db12-1175.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntigens, CD20B-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesDiabetes Mellitus, Type 1Interleukin-10Intestine, SmallMiceMice, Inbred NODConceptsT cellsNOD miceB cellsT cell-mediated autoimmune diseaseB cell-directed therapiesB cell depletion therapyCell-mediated autoimmune diseaseDiabetic NOD miceTransgenic NOD miceRegulatory T cellsCD4 T cellsCell-directed therapiesAnti-CD3 treatmentType 1 diabetesCD20 monotherapyImportant preclinical evidenceDepletion therapyT1D developmentDendritic cellsIL-10Preclinical evidenceFurther mechanistic studiesAutoimmune diseasesAnti-CD20Suppressive function
2010
Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens
Burton O, Gibbs S, Miller N, Jones F, Wen L, Dunne D, Cooke A, Zaccone P. Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens. European Journal Of Immunology 2010, 40: 2221-2229. PMID: 20480503, DOI: 10.1002/eji.200939998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, HelminthCD4-Positive T-LymphocytesCells, CulturedFemaleForkhead Transcription FactorsGalectin 3Helminth ProteinsHost-Pathogen InteractionsImmunomodulationLectins, C-TypeMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMinor Histocompatibility AntigensReceptors, Cell SurfaceSchistosoma mansoniToll-Like Receptor 2Transforming Growth Factor betaConceptsS. mansoni soluble egg antigenSchistosoma mansoni antigensT cellsFoxp3 expressionImportance of TLR2S. mansoni antigensSurface-bound TGFTLR2 ligand stimulationT cell secretionAccessory cell interactionsNOD miceTh2 responsesEgg antigenImmunomodulatory effectsT lymphocytesAbsence of APCC-type lectinBioactive TGFGalectin-3AntigenTGFTLR2Cell interactionsCellsLigand stimulation
2009
Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice
Hamilton-Williams EE, Martinez X, Clark J, Howlett S, Hunter KM, Rainbow DB, Wen L, Shlomchik MJ, Katz JD, Beilhack GF, Wicker LS, Sherman LA. Expression of Diabetes-Associated Genes by Dendritic Cells and CD4 T Cells Drives the Loss of Tolerance in Nonobese Diabetic Mice. The Journal Of Immunology 2009, 183: 1533-1541. PMID: 19592648, PMCID: PMC2733871, DOI: 10.4049/jimmunol.0900428.Peer-Reviewed Original ResearchConceptsRegulatory T cellsT cellsDendritic cellsNOD miceProtective allelesCD4 T-cell expressionTolerance defectsImmune tolerance resultsPancreatic lymph nodesCD8 T cellsNonobese diabetic (NOD) miceCD4 T cellsT cell expressionLoss of toleranceIL-2 productionDiabetes 3Lymph nodesDiabetic miceIslet AgsNOD alleleCell expressionMiceSpontaneous developmentIdd3Tolerance results
2008
Autoimmune syndrome after induction of neonatal tolerance to alloantigens: analysis of the role of donor T cells in the induction of autoimmunity
Merino J, Schurmans S, Wen L, Brighouse G, Luzuy S, Lambert P. Autoimmune syndrome after induction of neonatal tolerance to alloantigens: analysis of the role of donor T cells in the induction of autoimmunity. Clinical & Experimental Immunology 2008, 79: 273-278. PMID: 1968797, PMCID: PMC1534764, DOI: 10.1111/j.1365-2249.1990.tb05190.x.Peer-Reviewed Original ResearchConceptsDonor T cellsF1 donor B cellsDonor B cellsT cell subsetsAutoimmune syndromeF1 cellsT cellsNeonatal toleranceCell subsetsSpleen cellsNewborn miceB cellsBALB/c newborn miceMature donor T cellsDifferent T cell subsetsAutoreactive B cell clonesBALB/c miceLupus-like syndromeDeposits of immunoglobulinsF1 spleen cellsInduction of autoimmunityAnti-Sm antibodiesB cell clonesCTL alloreactivityTolerant mice
2006
Modulatory Role of DR4- to DQ8-restricted CD4 T-Cell Responses and Type 1 Diabetes Susceptibility
Ge X, Piganelli J, Tse H, Bertera S, Mathews C, Trucco M, Wen L, Rudert W. Modulatory Role of DR4- to DQ8-restricted CD4 T-Cell Responses and Type 1 Diabetes Susceptibility. Diabetes 2006, 55: 3455-3462. PMID: 17130492, DOI: 10.2337/db06-0680.Peer-Reviewed Original ResearchConceptsT cell responsesHLA moleculesCaucasian type 1 diabetic patientsCD4 T cell activityCD4 T cell linesCD4 T cell responsesType 1 diabetic patientsHLA class II allelesCertain HLA moleculesT cell activityType 1 diabetesClass II allelesT cell linesSpecific DRB1HLA-DQ8Diabetic patientsModulatory roleDisease riskDQ8Type 1DR4Diabetes susceptibilityPeptide occupancyPrimary genetic determinantGenetic determinants
2005
The Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice
Wong FS, Du W, Thomas IJ, Wen L. The Influence of the Major Histocompatibility Complex on Development of Autoimmune Diabetes in RIP-B7.1 Mice. Diabetes 2005, 54: 2032-2040. PMID: 15983204, DOI: 10.2337/diabetes.54.7.2032.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IHistocompatibility Antigens Class IIIslets of LangerhansLymphocyte DepletionMajor Histocompatibility ComplexMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDConceptsT cell repertoireMajor histocompatibility complexI-Ag7Autoimmune T cell repertoireImportant genetic susceptibility factorAutoreactive T cell repertoireBALB/c miceHistocompatibility complexNonobese-resistant miceRIP-B7.1 miceCD8 T cellsNonobese diabetic (NOD) miceMHC class II moleculesDiabetes-resistant miceType 1 diabetesIslet beta cellsClass II moleculesCostimulatory molecule B7.1MHC class IC57BL/6 genetic backgroundGenetic susceptibility factorsLocal costimulationAutoimmune diabetesNOD miceSpontaneous diabetes
2003
Critical roles of CD30/CD30L interactions in murine autoimmune diabetes
CHAKRABARTY S, NAGATA M, YASUDA H, WEN L, NAKAYAMA M, CHOWDHURY S, YAMADA K, JIN Z, KOTANI R, MORIYAMA H, SHIMOZATO O, YAGITA H, YOKONO K. Critical roles of CD30/CD30L interactions in murine autoimmune diabetes. Clinical & Experimental Immunology 2003, 133: 318-325. PMID: 12930356, PMCID: PMC1808783, DOI: 10.1046/j.1365-2249.2003.02223.x.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodies, MonoclonalAutoimmune DiseasesCD30 LigandCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, ExperimentalFemaleIslets of LangerhansKi-1 AntigenMaleMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDT-LymphocytesT-Lymphocytes, CytotoxicConceptsCD30/CD30L interactionIslet-specific CD4NOD miceDevelopment of diabetesT cell linesAutoimmune diabetesDiabetic NOD miceSpontaneous autoimmune diabetesPancreatic lymph nodesYoung NOD miceNOD-SCID miceT cell proliferationCD30/CD30LTumor necrosis factor receptorWeeks of ageCell linesNecrosis factor receptorMurine autoimmuneIslet antigensSpontaneous diabetesAdoptive transferLymph nodesEffector phaseT cellsSpleen cells
2002
Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide
Moriyama H, Wen L, Abiru N, Liu E, Yu L, Miao D, Gianani R, Wong F, Eisenbarth G. Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 5539-5544. PMID: 11943868, PMCID: PMC122805, DOI: 10.1073/pnas.082120099.Peer-Reviewed Original ResearchConceptsT lymphocytesB7-1 transgenic miceBALB/c miceAnti-islet autoimmunityExperimental autoimmune diabetesAutoreactive T lymphocytesB7-1 moleculeCD4 T lymphocytesType 1 diabetesPolyinosinic-polycytidylic acidAutoimmune diabetesInsulin autoantibodiesC micePeptide immunizationSimultaneous administrationDisease inductionMurine modelMouse modelDiabetesTransgenic miceInsulin peptidesMiceImmunizationPolyICViral mimic
2001
The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model
Wen L, Chen N, Tang J, Sherwin R, Wong F. The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model. Journal Of Clinical Investigation 2001, 107: 871-880. PMID: 11285306, PMCID: PMC199575, DOI: 10.1172/jci11708.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationDiabetes Mellitus, Type 1Disease Models, AnimalFemaleGene ExpressionHistocompatibility Antigens Class IIHLA-DQ AntigensHLA-DR4 AntigenIncidenceInsulinMaleMiceMice, Inbred C57BLMice, TransgenicMicrosatellite RepeatsPancreasSialadenitisSpleenTh2 CellsTransgenesConceptsMHC class II moleculesSpontaneous diabetesClass II moleculesTransgenic miceT cellsHLA-DQ8Diabetogenic effectMouse MHC class II moleculesHLA-DR transgenic miceTh2-like immune responsesHuman type 1 diabetesAutoreactive T cellsDouble transgenic miceType 1 diabetesC57BL/6 transgenic miceTh2-like phenotypePancreatic beta cellsExpression of DR4DQ8 allelesDiabetes developmentCostimulatory moleculesHLA-DQImmune responseBeta cellsDiabetes
2000
In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes
Wen L, Wong F, Tang J, Chen N, Altieri M, David C, Flavell R, Sherwin R. In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes. Journal Of Experimental Medicine 2000, 191: 97-104. PMID: 10620608, PMCID: PMC2195792, DOI: 10.1084/jem.191.1.97.Peer-Reviewed Original ResearchConceptsClass II moleculesMHC class II moleculesGlutamic acid decarboxylaseRat insulin promoterSpontaneous diabetesB7-1T cellsBeta cellsMouse MHC class II moleculesTransgenic miceHuman histocompatibility leukocyte antigenHuman type 1 diabetesMajor histocompatibility complex (MHC) class II moleculesCostimulatory molecules B7-1Human MHC class II moleculesVivo evidenceHistocompatibility leukocyte antigenDevelopment of diabetesType 1 diabetesMHC class IIC57BL/6 transgenic miceMurine MHC class IIPancreatic beta cellsVivo experimental evidenceDiabetogenic role
1998
The Role of Lymphocyte Subsets in Accelerated Diabetes in Nonobese Diabetic–Rat Insulin Promoter–B7-1 (NOD-RIP-B7-1) Mice
Wong F, Visintin I, Wen L, Granata J, Flavell R, Janeway C. The Role of Lymphocyte Subsets in Accelerated Diabetes in Nonobese Diabetic–Rat Insulin Promoter–B7-1 (NOD-RIP-B7-1) Mice. Journal Of Experimental Medicine 1998, 187: 1985-1993. PMID: 9625758, PMCID: PMC2212360, DOI: 10.1084/jem.187.12.1985.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAge of OnsetAnimalsAntigen PresentationB7-1 AntigenCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IIncidenceInsulinIslets of LangerhansLymphocyte SubsetsMiceMice, Inbred NODMice, TransgenicPromoter Regions, GeneticSpleenConceptsCD8 T cellsT cellsNOD miceB cellsAccelerated diabetesDiabetic miceB7-1 transgenic micePeripheral CD8 T cellsEffective antigen-presenting cellsMajor histocompatibility complex class IInsulin promoterCD4-/- miceMuMT-/- miceNontransgenic NOD miceNormal NOD miceNonobese diabetic (NOD) miceCD4 T cellsHistocompatibility complex class IAntigen-presenting cellsProvision of costimulationComplex class IPancreatic beta cellsWk of ageB220-positive B cellsIslet infiltrates
1996
T-cell alpha beta + and gamma delta + deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium.
Roberts S, Smith A, West A, Wen L, Findly R, Owen M, Hayday A. T-cell alpha beta + and gamma delta + deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 11774-11779. PMID: 8876213, PMCID: PMC38134, DOI: 10.1073/pnas.93.21.11774.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD4-Positive T-LymphocytesCoccidiosisEimeriaGastrointestinal HemorrhageIntestinal DiseasesIntestinal MucosaIntestine, SmallLymph NodesLymphocyte TransfusionMiceMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutPhenotypeReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaT-LymphocytesConceptsAlpha beta T cellsBeta T cellsT cellsGamma deltaT cell antigen receptorAlpha beta T-cell responsesT cell effector functionGamma delta T-cell antigen receptorsAlpha betaT cell responsesIntestinal damageProtective immunityAutoimmune diseasesEpithelial infectionDeficient miceEffector functionsEimeria vermiformisImmune systemCell responsesIntestinal epitheliumIntracellular protozoanWidespread infectionAntigen receptorInfectionMiceCD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.
Wong FS, Visintin I, Wen L, Flavell RA, Janeway CA. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. Journal Of Experimental Medicine 1996, 183: 67-76. PMID: 8551245, PMCID: PMC2192404, DOI: 10.1084/jem.183.1.67.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsB7-1 AntigenBase SequenceCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesClone CellsCytokinesDiabetes Mellitus, Type 2FemaleImmunohistochemistryImmunotherapy, AdoptiveInsulinIslets of LangerhansLymphocyte ActivationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDMolecular Sequence DataPancreasPerforinPore Forming Cytotoxic ProteinsPromoter Regions, GeneticConceptsT cell linesNOD miceT cellsCD8 T cell linesCD8 T cell clonesNonobese diabetic (NOD) miceCB17 SCID miceCD4 T cellsPathogenesis of diabetesT cell clonesCell linesIslets of LangerhansT cell antigen receptorNOD isletsCD4 cellsLymphocytic infiltrateNOD-SCIDDiabetic miceDiabetic isletsFemale NODRapid onsetCell antigen receptorH-2KdAntigen receptorMice
1991
Transient T and B cell activation after neonatal induction of tolerance to MHC class II or Mls alloantigens.
Schurmans S, Brighouse G, Kramer G, Wen L, Izui S, Merino J, Lambert P. Transient T and B cell activation after neonatal induction of tolerance to MHC class II or Mls alloantigens. The Journal Of Immunology 1991, 146: 2152-60. PMID: 1672344, DOI: 10.4049/jimmunol.146.7.2152.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntibodies, AntinuclearAntigen-Antibody ComplexAntigens, Differentiation, T-LymphocyteAntigens, SurfaceAutoimmune DiseasesB-LymphocytesCD4-Positive T-LymphocytesCD8 AntigensHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHypergammaglobulinemiaImmune ToleranceInterferon-gammaInterleukin-4Lymphocyte ActivationMajor Histocompatibility ComplexMiceMice, Inbred StrainsMinor Lymphocyte Stimulatory AntigensPlatelet CountReceptors, Antigen, T-CellThymus GlandT-LymphocytesConceptsMHC class IIB cell activationCell activationSpleen cellsClass IIAlloreactive CD4Neonatal injectionInjected miceT cellsF1 cellsTransient B cell activationIa AgLupus-like autoimmune syndromeSpecific toleranceClass IMajor histocompatibility complex class IFeatures of autoimmunityF1 spleen cellsTh cell responsesHistocompatibility complex class ICell-injected miceInduction of toleranceEarly postnatal periodComplex class IMHC class I