2019
Ruxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens
Carnes H, Mehrkens B, Stegman M, Rajagopalan G. Ruxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens. The Journal Of Immunology 2019, 202: 190.34-190.34. DOI: 10.4049/jimmunol.202.supp.190.34.Peer-Reviewed Original ResearchSystemic inflammatory response syndromeMulti-organ failureT cellsHLA-DR3 transgenic miceHLA class II moleculesVehicle-treated miceVivo studiesInflammatory response syndromeT cell subsetsToxic shock syndromeJAK 1/2 inhibitorSelective JAK1/2 inhibitorClass II moleculesStaphylococcus aureusDose-dependent mannerSerious diseaseJanus kinaseIL-17Response syndromeOrgan failureJAK1/2 inhibitorActivation markersCell subsetsShock syndromeIL-2
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
HLA-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 studiesCo-potentiation of antigen recognition: A mechanism to boost weak T cell responses and provide immunotherapy in vivo
Hoffmann M, Molina-Mendiola C, Nelson A, Parks C, Reyes E, Hansen M, Rajagopalan G, Pease L, Schrum A, Gil D. Co-potentiation of antigen recognition: A mechanism to boost weak T cell responses and provide immunotherapy in vivo. Science Advances 2015, 1: e1500415. PMID: 26601285, PMCID: PMC4646799, DOI: 10.1126/sciadv.1500415.Peer-Reviewed Original ResearchT cell responsesTCR/CD3T cell receptorWeak antigensCell responsesTCR/CD3 engagementWeak T cell responsesCD3 engagementMelanoma lung metastasisStrong immune responseAnti-melanoma immunotherapyImmune reactivityLung metastasesTherapeutic responseImmunotherapeutic designT cellsT lymphocytesImmune responseAdaptive immunityStrong antigenReceptor subunitsCell receptorAntigenCD3Antigen recognitionSuperantigens 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 bodyA monomeric fab fragment capable of inducing CD3 conformational change increases T cell receptor reactivity to poorly immunogenic antigens (TUM2P.1020)
Hoffmann M, Parks C, Hansen M, Rajagopalan G, Pease L, Schrum A, Gil Pages D. A monomeric fab fragment capable of inducing CD3 conformational change increases T cell receptor reactivity to poorly immunogenic antigens (TUM2P.1020). The Journal Of Immunology 2015, 194: 69.17-69.17. DOI: 10.4049/jimmunol.194.supp.69.17.Peer-Reviewed Original ResearchTCR/CD3Conformational changesCD3 complexT cell responsesProductive T cell responsesT cellsMature T cellsImmunogenic antigensCell responsesTCR engagementT cell activationTCR/MHC interactionsElicit signalingAnti-melanoma responsePMHC ligandsTg T cellsContext of vaccinationMonovalent Fab fragmentsMonomeric Fab fragmentsFab fragmentsSignal 2Cell activationPeptide ligandsCellsMetastatic melanoma
2014
Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome
Tilahun AY, Chowdhary VR, David CS, Rajagopalan G. Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome. The Journal Of Immunology 2014, 193: 2919-2930. PMID: 25092888, PMCID: PMC4157092, DOI: 10.4049/jimmunol.1400980.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodiesAntigen-Antibody ComplexEnterotoxinsGlucocorticoid-Induced TNFR-Related ProteinGlucocorticoidsHLA-DR alpha-ChainsHLA-DR beta-ChainsHLA-DR3 AntigenInterferon-gammaInterleukin-17Interleukin-2Lymphocyte ActivationMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicReceptors, Tumor Necrosis FactorShock, SepticStaphylococcal InfectionsSuperantigensT-Lymphocytes, RegulatoryUp-RegulationConceptsToxic shock syndromeEndogenous TregsRegulatory cellsShock syndromeT cellsGlucocorticoid-induced TNFR family-related receptorCommunity-acquired methicillin-resistant strainsEx vivoHLA-DR3 transgenic miceSerum IFN-γ levelsFailure of TregsSystemic inflammatory responseIL-2/T regulatory (Treg) cellsIFN-γ levelsConventional T cellsLife-threatening infectionsMethicillin-resistant strainsT cell activationS. aureus strainsTreg numbersAdoptive transferIL-17Immune activationInflammatory responseChronic activation with a staphylococcal superantigen drives the expansion of CD4, CD8 double negative T cells and promotes multiorgan inflammation mimicking systemic lupus erythematosus in HLA class II transgenic mice. (HUM7P.306)
Rajagopalan G, Tilahun A, Chowdhary V. Chronic activation with a staphylococcal superantigen drives the expansion of CD4, CD8 double negative T cells and promotes multiorgan inflammation mimicking systemic lupus erythematosus in HLA class II transgenic mice. (HUM7P.306). The Journal Of Immunology 2014, 192: 184.15-184.15. DOI: 10.4049/jimmunol.192.supp.184.15.Peer-Reviewed Original ResearchSystemic lupus erythematosusDNT cellsT cellsDKO miceLupus erythematosusKnockout miceCD8 coreceptorCD8 double-negative T cellsHLA class II transgenic miceTransgenic miceDouble-negative T cellsHLA-DR3 transgenic miceII transgenic miceRole of superantigensExpansion of CD4Role of CD4Negative T cellsLupus-like diseaseMini-osmotic pumpsPathogenesis of lupusWild-type miceSingle knockout miceDouble knockout miceT cell activationStaphylococcal enterotoxin B
2012
Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus
Chowdhary VR, Tilahun AY, Clark CR, Grande JP, Rajagopalan G. Chronic Exposure to Staphylococcal Superantigen Elicits a Systemic Inflammatory Disease Mimicking Lupus. The Journal Of Immunology 2012, 189: 2054-2062. PMID: 22798666, PMCID: PMC3462343, DOI: 10.4049/jimmunol.1201097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensAutoimmune DiseasesCD28 AntigensCD4-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFlow CytometryFluorescent Antibody TechniqueHLA-DQ AntigensHumansInfusions, SubcutaneousLupus Erythematosus, SystemicMiceMice, TransgenicStaphylococcus aureusSuperantigensConceptsSystemic lupus erythematosusT cellsChronic exposureStaphylococcal enterotoxin BLupus erythematosusMouse MHC class II moleculesHLA-DQ8 transgenic miceMultisystem autoimmune inflammatory diseaseEnterotoxin BHLA-DQ8 miceAutoimmune inflammatory diseaseMHC class II moleculesTh1-type cytokinesMini-osmotic pumpsMononuclear cell infiltrationAnti-nuclear AbsClass II moleculesAbsence of diseaseChronic nasalIL-12Inflammatory infiltrateAutoimmune diseasesCell infiltrationInflammatory diseasesPathogenic role
2011
Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB
Tilahun M, Kwan A, Natarajan K, Quinn M, Tilahun A, Xie C, Margulies D, Osborne B, Goldsby R, Rajagopalan G. Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB. PLOS ONE 2011, 6: e27203. PMID: 22102880, PMCID: PMC3216929, DOI: 10.1371/journal.pone.0027203.Peer-Reviewed Original ResearchConceptsToxic shock syndromeLethal toxic shock syndromeHLA-DR3 transgenic miceStaphylococcal enterotoxin BChimeric human-mouse antibodyShock syndromeT cellsVivo protectionTransgenic micePartial protectionComplete protectionLethal dosesT cell populationsClass II MHCSignificant partial protectionAnti-SEB antibodiesHuman T cellsOnly partial protectionInflammatory cytokinesClinical safetyII MHCB antibodiesVivo modelChimeric antibodyEnterotoxin BHLA-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 mimicry
2008
Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice
Rajagopalan G, Epstein B, Lytle A, David C. Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice. The FASEB Journal 2008, 22: 848.11-848.11. DOI: 10.1096/fasebj.22.1_supplement.848.11.Peer-Reviewed Original ResearchToxic shock syndromeRegulatory T cellsHLA-DR3 transgenic miceT cellsTransgenic miceHLA class II transgenic miceDepletion of TregsII transgenic miceSerum cytokine levelsStaphylococcal enterotoxin BTreg cellsCytokine levelsIL-17Regulatory cellsSEB challengeIL-21IL-22Systemic exposureIL-6Shock syndromeIL-2IL-2RSplenic expressionTGF-b1Toxic shock
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 modelDistinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes
Rajagopalan G, Mangalam A, Sen M, Kudva Y, David C. Distinct local immunogenic stimuli dictate differential requirements for CD4+ and CD8+ T cell subsets in the pathogenesis of spontaneous autoimmune diabetes. Autoimmunity 2007, 40: 489-496. PMID: 17966038, DOI: 10.1080/08916930701649836.Peer-Reviewed Original ResearchConceptsIncidence of diabetesPathogenesis of T1DRat insulin promoterTransgenic mouse modelMouse modelHLA-DQ8 transgenic miceMurine type 1 diabetesDouble transgenic mouse modelMHC class II associationsLocal inflammatory stimuliSpontaneous autoimmune diabetesT cell subsetsClass II associationsType 1 diabetesAutoimmune diabetesImmunogenic stimulusProinflammatory cytokinesCell subsetsCostimulatory moleculesTNF-alphaT cellsInflammatory stimuliDiabetesTransgenic miceCD4
2006
Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B—Implications for menstrual shock
Rajagopalan G, Smart M, Murali N, Patel R, David C. Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B—Implications for menstrual shock. Journal Of Reproductive Immunology 2006, 73: 51-59. PMID: 17070600, DOI: 10.1016/j.jri.2006.06.007.Peer-Reviewed Original ResearchConceptsMenstrual toxic shock syndromeSystemic immune activationHLA class II transgenic miceStaphylococcal enterotoxin BII transgenic miceImmune activationToxic shock syndromeSuperantigenic exotoxinsShock syndromeVaginal administrationTransgenic miceAcute systemic inflammatory diseaseSystemic inflammatory diseaseToxic shock syndrome toxinPeripheral lymphoid organsSEB-reactiveVaginal exposureProinflammatory cytokinesConjunctival routeLeukocytic infiltrationProfound elevationInflammatory diseasesLymphoid organsStaphylococcal superantigensT cellsINTRANASAL EXPOSURE TO STAPHYLOCOCCAL ENTEROTOXIN B ELICITS AN ACUTE SYSTEMIC INFLAMMATORY RESPONSE
Rajagopalan G, Sen M, Singh M, Murali N, Nath K, Iijima K, Kita H, Leontovich A, Gopinathan U, Patel R, David C. INTRANASAL EXPOSURE TO STAPHYLOCOCCAL ENTEROTOXIN B ELICITS AN ACUTE SYSTEMIC INFLAMMATORY RESPONSE. Shock 2006, 25: 647-656. PMID: 16721274, DOI: 10.1097/01.shk.0000209565.92445.7d.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesEnterotoxinsGene Expression RegulationHLA-DR3 AntigenHumansInflammationLungMiceMice, KnockoutNeutrophil InfiltrationReceptors, Interleukin-2Receptors, Interleukin-4Signal TransductionSystemic Inflammatory Response SyndromeConceptsII transgenic miceHLA class II transgenic miceStaphylococcal enterotoxin BCD8 T cellsTransgenic miceIntranasal exposureIL-12T cellsIFN-gammaEndogenous class II moleculesSystemic inflammatory response syndromeTCR V beta 8Defective IL-12Serum IFN-gammaSystemic immune activationInflammatory response syndromeSystemic cytokine responseBronchoalveolar lavage fluidMononuclear cell infiltrationPoor immune responsePro-inflammatory cytokinesS. aureus colonizationClass II moleculesIL-4 receptorNeutrophil influx
2005
Endogenous Superantigens Shape Response to Exogenous Superantigens
Rajagopalan G, Singh M, Sen M, Murali N, Nath K, David C. Endogenous Superantigens Shape Response to Exogenous Superantigens. MSphere 2005, 12: 1119-1122. PMID: 16148182, PMCID: PMC1235787, DOI: 10.1128/cdli.12.9.1119-1122.2005.Peer-Reviewed Original Research