2024
Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation
Hanin A, Comi M, Sumida T, Hafler D. Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation. Life Science Alliance 2024, 7: e202402890. PMID: 39366761, PMCID: PMC11452476, DOI: 10.26508/lsa.202402890.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cellsEffector/memory cellsCentral nervous system milieuT cell environmentCD4 T cellsIFNG mRNA expressionCXCR3<sup>+</sup> cellsT cell homeostasisInhibition of SGK1Targeting lipid pathwaysMaintenance of immune surveillanceSerum/glucocorticoid-regulated kinaseImmune surveillanceHealthy donorsCytotoxic capacityEffector responsesInflammatory conditionsSGK1 activityMRNA expressionNervous systemSGK1Metabolic conditionsLipid pathwaysTissue adaptation
2023
Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.Peer-Reviewed Original ResearchConceptsB cell depletion therapyAcute COVID infectionAnti-spike IgGHigh-risk patientsCoronavirus disease-19COVID-19 pathologyDepletion therapyVaccine protectionAntibody responseCOVID infectionHematologic malignanciesImmune protectionDisease-19Healthy donorsMultiple time pointsSerology assaysBlood samplesSoluble markersB cellsImmunization strategiesPatientsFunctional deficiencySerological analysisTime pointsClonotype diversity
2021
Oleic acid restores suppressive defects in tissue-resident FOXP3 regulatory T cells from patients with multiple sclerosis
Pompura SL, Wagner A, Kitz A, Laperche J, Yosef N, Dominguez-Villar M, Hafler D. Oleic acid restores suppressive defects in tissue-resident FOXP3 regulatory T cells from patients with multiple sclerosis. Journal Of Clinical Investigation 2021, 131 PMID: 33170805, PMCID: PMC7810477, DOI: 10.1172/jci138519.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAdipose tissueFoxp3 regulatory T cellsExpression of Foxp3Regulatory T cellsTreg suppressive functionProinflammatory arachidonic acidHuman adipose tissuePhosphorylation of STAT5Treg homeostasisFatty acidsPeripheral bloodTissue residencyHealthy donorsInflammatory signalsT cellsTregsFree fatty acidsSuppressive functionArachidonic acidPatientsOleic acidOxidative phosphorylationTranscriptomic programsFoxp3
2020
Transcriptomic and clonal characterization of T cells in the human central nervous system
Pappalardo JL, Zhang L, Pecsok MK, Perlman K, Zografou C, Raddassi K, Abulaban A, Krishnaswamy S, Antel J, van Dijk D, Hafler DA. Transcriptomic and clonal characterization of T cells in the human central nervous system. Science Immunology 2020, 5 PMID: 32948672, PMCID: PMC8567322, DOI: 10.1126/sciimmunol.abb8786.Peer-Reviewed Original ResearchConceptsCentral nervous systemCSF of patientsT cellsCerebrospinal fluidMultiple sclerosisImmune surveillanceNervous systemCSF T cellsHuman central nervous systemHealthy human donorsT cell activationImmune dysfunctionNeuroinflammatory diseasesCytotoxic capacityHealthy donorsHealthy individualsCell activationHuman donorsTissue adaptationPatientsClonal characterizationExpression of genesCellsSurveillanceFurther characterizationDifferential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiforme
2017
Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme
Goods BA, Hernandez AL, Lowther DE, Lucca LE, Lerner BA, Gunel M, Raddassi K, Coric V, Hafler DA, Love JC. Functional differences between PD-1+ and PD-1- CD4+ effector T cells in healthy donors and patients with glioblastoma multiforme. PLOS ONE 2017, 12: e0181538. PMID: 28880903, PMCID: PMC5589094, DOI: 10.1371/journal.pone.0181538.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-1 expressionEffector T cellsPD-1Effector cellsGlioblastoma multiformeCheckpoint inhibitorsTim-3T cellsHealthy subjectsCell death protein 1Features of exhaustionDeath protein 1T cell compartmentContext of GBMRecovery of functionCD4 effectorsCD4 cellsRNA sequencingTreatment of cancerHealthy donorsGBM patientsBrain cancerCD4Tumors
2015
CBM-05FUNCTIONAL DIFFERENCES BETWEEN PD-1+ AND PD-1– CD4+ T EFFECTOR CELLS IN HEALTHY DONORS AND PATIENTS WITH GLIOBLASTOMA
Goods B, Lowther D, Lucca L, Hernandez A, Lerner B, Gunel M, Raddassi K, Simon J, Coric V, Love J, Hafler D. CBM-05FUNCTIONAL DIFFERENCES BETWEEN PD-1+ AND PD-1– CD4+ T EFFECTOR CELLS IN HEALTHY DONORS AND PATIENTS WITH GLIOBLASTOMA. Neuro-Oncology 2015, 17: v70-v70. PMCID: PMC4638709, DOI: 10.1093/neuonc/nov211.05.Peer-Reviewed Original Research
2008
Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis
Vaknin-Dembinsky A, Murugaiyan G, Hafler DA, Astier AL, Weiner HL. Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis. Journal Of Neuroimmunology 2008, 195: 140-145. PMID: 18403025, PMCID: PMC2702859, DOI: 10.1016/j.jneuroim.2008.01.002.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCentral nervous systemChemokine productionHealthy donorsCD46 activationPathogenesis of MSIL-23 secretionChronic inflammatory diseasePotent proinflammatory cytokineRole of CD46CCL2 levelsDC activationIL-23Dendritic cellsIL-23p19Proinflammatory cytokinesCCL5 productionInflammatory diseasesNervous systemPatientsPotential roleSclerosisCytokinesActivationElevated amounts
2004
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis. Journal Of Experimental Medicine 2004, 199: 971-979. PMID: 15067033, PMCID: PMC2211881, DOI: 10.1084/jem.20031579.Peer-Reviewed Original ResearchConceptsRegulatory T cellsMultiple sclerosisT cellsRegulatory T cell functionActivity of murineSpontaneous autoimmune diseaseT cell functionSingle cell cloning experimentsPeripheral toleranceCell cloning experimentsAutoimmune diseasesPeripheral bloodInflammatory diseasesHealthy donorsHuman CD4Effector functionsNormal controlsPatientsFunctional suppressionCell functionSignificant decreaseSclerosisProtein peptidesDiseaseActive suppression