2018
Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice
Rajagopalan G, Krogman A, Chowdhary V. Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice. The Journal Of Immunology 2018, 200: 117.3-117.3. DOI: 10.4049/jimmunol.200.supp.117.3.Peer-Reviewed Original ResearchHLA-DR3 transgenic miceToxic shock syndromeIL-17Transgenic miceHLA-DR3Shock syndromeAdaptive T cell responsesStaphylococcal toxic shock syndromeIL-17 family membersT cell responsesRole of IFNStaphylococcus aureus infectionS. aureusNon-specific activationTh17 cellsSerum levelsHLA-DRMice succumbedSystemic elevationTh1 cellsAureus infectionTissue injuryT cellsInfectious agentsIFN
2017
Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen
Chowdhary VR, Krogman A, Tilahun AY, Alexander MP, David CS, Rajagopalan G. Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative αβ TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen. The Journal Of Immunology 2017, 198: 4413-4424. PMID: 28468970, PMCID: PMC5471834, DOI: 10.4049/jimmunol.1601991.Peer-Reviewed Original ResearchConceptsDNT cellsDKO miceClass II moleculesΑβ TCRT cellsBacterial superantigensCD8 coreceptorIntact MHC class ILupus-like autoimmune diseaseEnterotoxin BHLA-DQ8 moleculesMHC class II moleculesAnti-nuclear AbsPeripheral T cellsDouble knockout miceMurine MHC class II moleculesMHC class IThymic positive selectionStaphylococcal enterotoxin BCD4/CD8 coreceptorsRegulatory cellsHLA-DR3Splenic CD3WT miceAutoimmune diseases
2016
Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model
Sheen Y, Rajagopalan G, Snapper C, Kita H, Wi C, Umaretiya P, Juhn Y. Influence of HLA‐DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model. HLA 2016, 88: 25-34. PMID: 27506953, PMCID: PMC6326101, DOI: 10.1111/tan.12851.Peer-Reviewed Original ResearchConceptsHouse dust miteHumoral immune responseAnti-pneumococcal polysaccharideHLA-DR polymorphismImmune responseHDM sensitizationIntact pneumococciHLA-DR3IgG responsesSerum titersTransgenic miceIntranasal house dust miteAnti-phosphorylcholine IgMHLA-DR3 miceLower humoral immune responseHalf of miceTransgenic mouse modelAllergic sensitizationPneumococcal diseaseIgM responseDR3 miceDust mitePneumococcal polysaccharideMouse modelA-IgGHLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia.
Rajagopalan G, Karau M, Krogman A, Patel R, David C. HLA-DR3 transgenic mice expressing Nur77-GFP reveal early and robust activation of T cells by superantigens during Staphylococcus aureus pneumonia. The Journal Of Immunology 2016, 196: 66.9-66.9. DOI: 10.4049/jimmunol.196.supp.66.9.Peer-Reviewed Original ResearchSAg staphylococcal enterotoxin BT cell activationStaphylococcus aureus pneumoniaT cellsCell activationAureus pneumoniaStaphylococcal pneumoniaSerum cytokine/chemokine levelsCytokine/chemokine levelsHLA-DR3 transgenic miceT-cell activation markersEarly T cell activation markerRole of superantigensCell activation markersT cell subsetsTiming of administrationS. aureus strainsStaphylococcal enterotoxin BChemokine levelsDifferent time pointsHLA-DR3Activation markersCell subsetsCD69 expressionExperimental pneumonia
2015
Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model
Kim C, Karau M, Greenwood-Quaintance K, Tilahun A, Krogman A, David C, Pritt B, Patel R, Rajagopalan G. Superantigen-Producing Staphylococcus aureus Elicits Systemic Immune Activation in a Murine Wound Colonization Model. Toxins 2015, 7: 5308-5319. PMID: 26670252, PMCID: PMC4690136, DOI: 10.3390/toxins7124886.Peer-Reviewed Original ResearchConceptsSystemic immune activationImmune activationT cellsS. aureusSerum IL-17 levelsSystemic immunologic effectsIL-17 levelsSpleens of miceWound infection modelImmunologic effectsInflammatory changesHLA-DR3Wound infectionCommon causeTransgenic miceUninfected woundsDay 8Immune systemClinical implicationsInfection modelMiceSkin woundsWoundsMicrobial challengeStaphylococcus aureusA Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus
Chowdhary VR, Dai C, Tilahun AY, Hanson JA, Smart MK, Grande JP, Rajagopalan G, Fu SM, David CS. A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus. The Journal Of Immunology 2015, 195: 4660-4667. PMID: 26475924, PMCID: PMC5292932, DOI: 10.4049/jimmunol.1501073.Peer-Reviewed Original ResearchConceptsHLA-DR3NZM2328 miceClass IIMouse modelEndogenous MHC class IIAnti-dsDNA titersWire-loop lesionsSystemic lupus erythematosusSpecific HLA allelesMHC class IITransgenic mouse modelAnti-Sm AbsLupus erythematosusSevere proteinuriaAutoimmune responseHLA-DR2Lymphoid aggregatesAntibody responseHLA-DR3 moleculesHistological scoresT cellsImmune responseSpontaneous lupusHLA allelesHuman studiesSuperantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia
Chung J, Greenwood-Quaintance K, Karau MJ, Tilahun A, Khaleghi SR, Chowdhary VR, David CS, Patel R, Rajagopalan G. Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia. Journal Of Leukocyte Biology 2015, 98: 271-281. PMID: 25979434, PMCID: PMC4501677, DOI: 10.1189/jlb.4a1214-577rr.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatheter-Related InfectionsCatheters, IndwellingCD4-Positive T-LymphocytesEnterotoxinsGene DeletionHistocompatibility AntigensHumansKidneyLiverLungLymphocyte ActivationMiceMice, TransgenicReceptors, Antigen, T-Cell, alpha-betaSpleenStaphylococcal InfectionsStaphylococcus aureusSuperantigensConceptsS. aureusHLA-DR3 transgenic miceLong intravenous catheterSystemic immune activationSerum cytokine levelsSystemic inflammatory diseaseAbsence of bacteremiaMHC class II moleculesInvasive staphylococcal diseaseToxigenic S. aureusClinical S. aureus isolatesS. aureus isolatesClass II moleculesIsogenic S. aureusCytokine levelsHLA-DR3Immune activationInflammatory diseasesIntravenous cathetersStaphylococcal diseaseRole of SAgsDevice-associated infectionsT cellsClinical consequencesForeign body
2014
The Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia
Tilahun A, Karau M, Ballard A, Gunaratna M, Thapa A, David C, Patel R, Rajagopalan G. The Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia. Mediators Of Inflammation 2014, 2014: 468285. PMID: 25024509, PMCID: PMC4082930, DOI: 10.1155/2014/468285.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsHLA-DQ8 transgenic miceHeat-killed Staphylococcus aureusToxic shock syndromeStaphylococcal superantigensHLA-DR3Shock syndromeMolecular patternsTransgenic miceS. aureus-derived peptidoglycanSerious S. aureus infectionsCytokine/chemokine responsesLipoteichoic acidStaphylococcal toxic shock syndromeS. aureusLife-threatening systemic diseaseAnti-inflammatory roleT cell expansionS. aureus infectionT cell proliferationToxigenic S. aureusStaphylococcus aureusAdaptive immune systemChemokine responsesSystemic disease
2011
HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD
Deshmukh U, Sim D, Dai C, Kannapell C, Gaskin F, Rajagopalan G, David C, Fu S. HLA-DR3 restricted T cell epitope mimicry in induction of autoimmune response to lupus-associated antigen SmD. Journal Of Autoimmunity 2011, 37: 254-262. PMID: 21868195, PMCID: PMC3372418, DOI: 10.1016/j.jaut.2011.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAutoantibodiesAutoantigensAutoimmunityEpitopes, T-LymphocyteFemaleHLA-DR3 AntigenHumansHybridomasImmunizationLupus Erythematosus, SystemicLymphocyte ActivationMiceMice, TransgenicMolecular MimicryPeptidesProtein BindingSnRNP Core ProteinsStreptococcus agalactiaeT-LymphocytesVibrio choleraeConceptsSystemic lupus erythematosusHLA-DR3 transgenic miceT cell epitopesHLA-DR3T cellsEpitope levelCell epitopesTransgenic miceMolecular mimicryPathogenesis of SLET cell epitope mimicryAutoreactive T cell clonesT hybridomasHLA-DR3 miceMicrobial peptidesAutoreactive T cellsProduction of autoantibodiesT cell responsesT cell clonesLupus erythematosusLupus autoantigensAutoimmune responseAutoimmune disordersImmunized miceEpitope mimicryHLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation
Rajagopalan G, Tilahun A, Iijima K, David C, Kita H, Juhn Y. HLA‐DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation. HLA 2011, 77: 589-592. PMID: 21447115, DOI: 10.1111/j.1399-0039.2010.01617.x.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceHouse dust miteDust miteTransgenic miceTh2-predominant immune responseHouse dust mite extractInterleukin-13 levelsInflammatory cell countsBronchoalveolar lavage fluidTh2-type inflammationTransgenic mouse modelHLA-DR polymorphismAirway inflammationCytokine levelsBAL fluidEosinophil countHLA-DR3Childhood asthmaHLA-DR2Lavage fluidMite extractHLA-DRB1Immune responseInterleukin-4Mouse model
2007
Chronic low-grade exposure to bacterial superantigens elicits sustained T cell expansion and multiorgan inflammation. Implications for autoimmunity. (130.22)
Rajagopalan G, Smart M, Grande J, David C. Chronic low-grade exposure to bacterial superantigens elicits sustained T cell expansion and multiorgan inflammation. Implications for autoimmunity. (130.22). The Journal Of Immunology 2007, 178: s232-s232. DOI: 10.4049/jimmunol.178.supp.130.22.Peer-Reviewed Original ResearchBacterial superantigensT cellsChronic exposureHLA-DQ8 transgenic miceIntense perivascular infiltrationLow-grade exposurePercentage of CD8MHC class II moleculesAntigen non-specific mannerT cell expansionToxic shock syndromeMHC class IITransgenic mouse modelClass II moleculesMurine MHC class IIPerivascular infiltrationHLA-DR3Inflammatory infiltrateMiniosmotic pumpsShock syndromeImmunological outcomesAcute diseaseMultiorgan inflammationHistological examinationMouse model
2003
Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans
Rajagopalan G, Kudva YC, Chen L, Wen L, David CS. Autoimmune diabetes in HLA‐DR3/DQ8 transgenic mice expressing the co‐stimulatory molecule B7‐1 in the β cells of islets of Langerhans. International Immunology 2003, 15: 1035-1044. PMID: 12917255, DOI: 10.1093/intimm/dxg103.Peer-Reviewed Original ResearchConceptsCo-stimulatory molecules B7-1Incidence of diabetesTransgenic miceB7-1Autoimmune diabetesHLA-DQ8HLA-DR3T cellsBeta cellsBeta-cell toxin streptozotocinHLA class II associationsDQ8 transgenic micePresence of DR3HLA transgenic miceAntibody-mediated depletionPathogenesis of T1D.Class II associationsHLA class IIWhole-body irradiationPancreatic beta cellsNon-specific activationSpontaneous diabetesToxin streptozotocinDiabetogenic potentialSTZ treatment
2002
Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II
Kudva Y, Rajagopalan G, Raju R, Abraham R, Smart M, Hanson J, David C. Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II. Human Immunology 2002, 63: 987-999. PMID: 12392851, DOI: 10.1016/s0198-8859(02)00435-4.Peer-Reviewed Original ResearchConceptsType 1 diabetesEndogenous class II moleculesClass II moleculesHLA-DR3NOD miceHuman leukocyte antigen (HLA) transgenic miceTransgenic miceEndogenous MHC class IICyclophosphamide-induced diabetesIntra-islet infiltrationMultiple low dosesDouble transgenic miceGroups of miceMHC class IINonobese diabetic (NOD) backgroundTransgenic expressionSpontaneous diabetesDiabetic backgroundUnmanipulated miceDQ8DiabetesLow dosesClass IILess infiltrationMice