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
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‐DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin‐1 in a transgenic mouse model
Krogman A, Tilahun A, David CS, Chowdhary VR, Alexander MP, Rajagopalan G. HLA‐DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin‐1 in a transgenic mouse model. HLA 2016, 89: 20-28. PMID: 27863161, DOI: 10.1111/tan.12930.Peer-Reviewed Original ResearchToxic shock syndrome toxin-1Class II moleculesMHC class II moleculesHLA-DR allelesSyndrome toxin-1Transgenic miceImmune activationHuman leukocyte antigen (HLA) transgenic miceSpecific HLA class II allelesToxin 1Cytokine/chemokine responsesMajor histocompatibility complex (MHC) class II moleculesNonmenstrual toxic shock syndromeDifferent HLA-DR allelesHLA class II allelesStaphylococcal toxic shock syndrome toxin 1Severe organ pathologyDifferent HLA-DRB1 allelesMultiple immune parametersT cell expansionHLA-DRB1 allelesToxic shock syndromeTransgenic mouse modelOutcome of diseaseClass II alleles
2015
Superantigens 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
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
Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome
Tilahun A, Marietta E, Wu T, Patel R, David C, Rajagopalan G. Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome. American Journal Of Pathology 2011, 178: 2760-2773. PMID: 21641398, PMCID: PMC3124354, DOI: 10.1016/j.ajpath.2011.02.033.Peer-Reviewed Original ResearchConceptsToxic shock syndromeShock syndromeTransgenic miceSmall intestineHLA-DR3 transgenic miceHLA class II moleculesMultiple organ inflammationPotent T cell activatorsKey pathogenic eventClass II moleculesT cell activatorsGut dysfunctionKawasaki diseaseLiver failureHeavy infiltrationHigh morbidityD-GalN.Pathologic changesT lymphocytesExtrahepatic pathologyPathogenic eventsAbsorptive functionD-galactosamineSensitization modelMouse strains
2008
HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases
Mangalam A, Rajagopalan G, Taneja V, David C. HLA Class II Transgenic Mice Mimic Human Inflammatory Diseases. Advances In Immunology 2008, 97: 65-147. PMID: 18501769, DOI: 10.1016/s0065-2776(08)00002-3.Peer-Reviewed Original ResearchConceptsHLA class II transgenic miceClass II moleculesII transgenic miceCommon autoimmune diseaseAutoimmune diseasesInflammatory diseasesTransgenic miceClass II genesDQ allelesHLA class II associationsInsulin-dependent diabetes mellitusHLA class II moleculesHLA transgenic miceCD4 T cellsClass II associationsHuman class II moleculesAutoimmune disease developmentToxic shock syndromeT cell repertoireHLA class II genesHuman inflammatory diseasesSimilar antigenic epitopesMHC class II genesAutoimmune myocarditisDiabetes mellitus
2007
Evaluating the role of HLA‐DQ polymorphisms on immune response to bacterial superantigens using transgenic mice
Rajagopalan G, Polich G, Sen M, Singh M, Epstein B, Lytle A, Rouse M, Patel R, David C. Evaluating the role of HLA‐DQ polymorphisms on immune response to bacterial superantigens using transgenic mice. HLA 2007, 71: 135-145. PMID: 18086265, DOI: 10.1111/j.1399-0039.2007.00986.x.Peer-Reviewed Original ResearchConceptsStreptococcal mitogenic exotoxin ZClass II moleculesHLA class II moleculesHLA-DQ6HLA-DQ8Transgenic miceBacterial superantigensImmune responseHLA class II transgenic miceHLA-DQ8 transgenic miceHuman leukocyte antigen (HLA) class II moleculesHLA class II allelesToxic shock syndrome toxin-1II transgenic miceSimilar clinical outcomesHLA-DQ polymorphismStreptococcal pyrogenic exotoxin AHLA class IIVivo immune responseHLA class II polymorphismClass II allelesPyrogenic exotoxin ASyndrome toxin-1Superantigen-mediated diseasesClass II polymorphismChronic 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
2006
INTRANASAL 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
2004
In Vitro and In Vivo Evaluation of Staphylococcal Superantigen Peptide Antagonists
Rajagopalan G, Sen M, David C. In Vitro and In Vivo Evaluation of Staphylococcal Superantigen Peptide Antagonists. Infection And Immunity 2004, 72: 6733-6737. PMID: 15501813, PMCID: PMC522998, DOI: 10.1128/iai.72.11.6733-6737.2004.Peer-Reviewed Original Research
2003
Expression and function of HLA‐DR3 and DQ8 in transgenic mice lacking functional H2‐M
Rajagopalan G, Smart M, Cheng S, Krco C, Johnson K, David C. Expression and function of HLA‐DR3 and DQ8 in transgenic mice lacking functional H2‐M. HLA 2003, 62: 149-161. PMID: 12889995, DOI: 10.1034/j.1399-0039.2003.00088.x.Peer-Reviewed Original ResearchAccelerated Diabetes in Rat Insulin Promoter-Tumor Necrosis Factor-α Transgenic Nonobese Diabetic Mice Lacking Major Histocompatibility Class II Molecules
Rajagopalan G, Kudva YC, Flavell RA, David CS. Accelerated Diabetes in Rat Insulin Promoter-Tumor Necrosis Factor-α Transgenic Nonobese Diabetic Mice Lacking Major Histocompatibility Class II Molecules. Diabetes 2003, 52: 342-347. PMID: 12540606, DOI: 10.2337/diabetes.52.2.342.Peer-Reviewed Original ResearchConceptsClass II moleculesNecrosis factorT cellsHLA class II associationsHuman type 1 diabetesMajor histocompatibility class II moleculesFunctional class II moleculesClass II associationsType 1 diabetesRat insulin promoterTumor necrosis factorLocal proinflammatory environmentIslets of LangerhansAccelerated diabetesNOD miceHLA-DQ8Proinflammatory environmentC57BL/6 miceTNF-alphaDiabetesDisease pathogenesisSignificant protectionMajor histocompatibility complex locusNeonatal expressionMice
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 infiltrationMiceExpression and Function of Transgenic HLA-DQ Molecules and Lymphocyte Development in Mice Lacking Invariant Chain
Rajagopalan G, Smart M, Krco C, David C. Expression and Function of Transgenic HLA-DQ Molecules and Lymphocyte Development in Mice Lacking Invariant Chain. The Journal Of Immunology 2002, 169: 1774-1783. PMID: 12165499, DOI: 10.4049/jimmunol.169.4.1774.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigensAntigens, Differentiation, B-LymphocyteB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCytoskeletal ProteinsEnterotoxinsGene ExpressionHistocompatibility Antigens Class IIHLA-DQ AntigensHumansIn Vitro TechniquesInterferon-gammaLymphocyte ActivationLymphocyte SubsetsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicShock, SepticConceptsClass II moleculesStaphylococcal enterotoxin BMHC class II moleculesT cellsFunctional MHC class II moleculesSystemic IFN-gamma productionT cell responsesHuman class II moleculesIFN-gamma productionPrimed T cellsHLA-DQ moleculesInvariant chainSpecific T cell hybridomasProcessing/presentationT cell hybridomasT cell developmentDQ8 miceExogenous superantigensHLA-DQ8Mature B cellsCytokine productionHLA-DQ6Phenotype of miceVivo challengeB cells