2008
CTLA4Ig treatment in patients with multiple sclerosis
Viglietta V, Bourcier K, Buckle GJ, Healy B, Weiner HL, Hafler DA, Egorova S, Guttmann CR, Rusche JR, Khoury SJ. CTLA4Ig treatment in patients with multiple sclerosis. Neurology 2008, 71: 917-924. PMID: 18794494, DOI: 10.1212/01.wnl.0000325915.00112.61.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCostimulatory pathwayPhase 1 dose-escalation studyT cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseRelapsing-remitting multiple sclerosisT-cell costimulatory pathwaysCostimulatory molecule interactionsMonths of infusionDose-escalation studyInterferon-gamma productionT cell activationOriginal therapeutic approachAdverse eventsImmunologic assessmentImmunologic effectsCTLA4Ig treatmentChronic inflammationAutoimmune diseasesInflammatory processT cellsImmune responseTherapeutic approachesCTLA4IgExtension study
2003
Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*
Slavik JM, Lim DG, Burakoff SJ, Hafler DA. Rapamycin-resistant Proliferation of CD8+ T Cells Correlates with p27 kip1 Down-regulation and bcl-xL Induction, and Is Prevented by an Inhibitor of Phosphoinositide 3-Kinase Activity*. Journal Of Biological Chemistry 2003, 279: 910-919. PMID: 14573608, DOI: 10.1074/jbc.m209733200.Peer-Reviewed Original ResearchMeSH KeywordsAnnexin A5Antibiotics, AntineoplasticBcl-X ProteinCD28 AntigensCD3 ComplexCD8-Positive T-LymphocytesCell Cycle ProteinsCell DivisionColoring AgentsCyclin DCyclin-Dependent Kinase Inhibitor p27CyclinsDose-Response Relationship, DrugDown-RegulationEnzyme InhibitorsEstersFluoresceinsHumansKineticsLymphocytesPhosphatidylinositol 3-KinasesProtein BindingProto-Oncogene Proteins c-bcl-2Signal TransductionSirolimusT-LymphocytesTime FactorsTumor Suppressor ProteinsConceptsInhibitor of phosphoinositideT cell receptorMammalian cell typesCell receptorBcl-xL inductionAction of rapamycinBcl-xL expressionT cellsHuman cellsCell survivalP27 Kip1Resistant proliferationCell typesPhosphoinositideHuman CD8RapamycinCellular proliferationEffect of rapamycinMicrobial infectionsCell populationsHigh-affinity T-cell receptorsSelective immunosuppressive effectT Cells CorrelateT cell populationsProliferationIn vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis
Schmied M, Duda PW, Krieger JI, Trollmo C, Hafler DA. In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis. Clinical Immunology 2003, 106: 163-174. PMID: 12706402, DOI: 10.1016/s1521-6616(03)00020-2.Peer-Reviewed Original ResearchConceptsGA-reactive T cellsT cell reactivityT cellsRR-MSMultiple sclerosisCell reactivityT cell peripheral toleranceTh2-type T cellsT cell frequenciesMonths of treatmentT cell hyporesponsivenessT cell populationsT cell nonresponsivenessT cell anergyHyporesponsive T cellsMechanism of actionMyelin antigensGlatiramer acetatePeripheral toleranceCell hyporesponsivenessPeripheral bloodClonal eliminationIL-2Cell anergySubcutaneous administration
2001
Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes
Slavik J, Lim D, Burakoff S, Hafler D. Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes. The Journal Of Immunology 2001, 166: 3201-3209. PMID: 11207273, DOI: 10.4049/jimmunol.166.5.3201.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalCD2 AntigensCD28 AntigensCD3 ComplexCD8 AntigensCD8-Positive T-LymphocytesCell Line, TransformedClone CellsDose-Response Relationship, DrugDose-Response Relationship, ImmunologicDrug ResistanceEnzyme ActivationEpitopes, T-LymphocyteHLA-A AntigensHumansImmunosuppressive AgentsInterleukin-2Lymphocyte ActivationMajor Histocompatibility ComplexModels, ImmunologicalRibosomal Protein S6 KinasesSirolimusT-Lymphocyte SubsetsConceptsT cell clonesT cellsEffect of rapamycinHuman T cell responsesPeripheral blood T cellsCell clonesHeterogeneous proliferative responsesT cell responsesBlood T cellsT cell proliferationSpecific costimulatory signalsGraft infiltrationResistant proliferationInhibition of AgGraft rejectionHuman CD8IL-2RT lymphocytesProliferative responseCostimulatory signalsCell responsesPresence of rapamycinCell proliferationRapamycinProliferation
1988
Cumulative Experience with High‐Dose Intravenous Cyclophosphamide and ACTH Therapy in Chronic Progressive Multiple Sclerosis
CARTER J, DAWSON D, HAFLER D, FALLIS R, STAZZONE L, ORAV J, WEINER H. Cumulative Experience with High‐Dose Intravenous Cyclophosphamide and ACTH Therapy in Chronic Progressive Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1988, 540: 535-536. PMID: 2849902, DOI: 10.1111/j.1749-6632.1988.tb27163.x.Peer-Reviewed Original ResearchMeSH KeywordsAdrenocorticotropic HormoneCyclophosphamideDose-Response Relationship, DrugHumansMultiple Sclerosis
1987
Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies.
Dawson DM, Carter JL, Hafler DA, Weiner HL. Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies. Nuova Rivista Di Neurologia 1987, 57: 88-91. PMID: 3039645.Peer-Reviewed Original ResearchMeSH KeywordsAdrenocorticotropic HormoneAntibodies, MonoclonalCyclophosphamideDose-Response Relationship, DrugHumansImmune ToleranceInfusions, IntravenousMultiple SclerosisT-LymphocytesConceptsProgressive multiple sclerosisMonoclonal antibody therapyMultiple sclerosisAntibody therapyChronic progressive multiple sclerosisHigh-dose intravenous cyclophosphamideMultiple sclerosis patientsForm of treatmentLong-term controlIntravenous cyclophosphamideSclerosis patientsClinical resultsSerious toxicityImmune parametersPilot trialCyclophosphamideNervous systemSclerosisTerm controlsPatientsMonoclonal antibodiesACTHOnly small numbersTherapyAdverse effects