2023
PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin toleranceHSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal
Pierce C, Loh L, Steach H, Cheshenko N, Preston-Hurlburt P, Zhang F, Stransky S, Kravets L, Sidoli S, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal. Journal Of Clinical Investigation 2023, 133: e164317. PMID: 37079384, PMCID: PMC10232005, DOI: 10.1172/jci164317.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV latency reversalT cellsLatency reversalHuman CD4HIV-1 viral loadHIV-1 restriction factorsHSV-2 recurrencesHSV-2 infectionHIV-1 latencyUpregulation of MALAT1Primary human CD4HSV-2 proteinsViral loadHIV replicationPeripheral bloodMALAT1 expressionHSV-2Tissue reservoirsCD4Viral replicationExpression of transcriptsBystander cellsRestriction factorsMALAT1Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations
Ren J, Qu R, Rahman N, Lewis J, King A, Liao X, Mirza F, Carlson K, Huang Y, Gigante S, Evans B, Rajendran B, Xu S, Wang G, Foss F, Damsky W, Kluger Y, Krishnaswamy S, Girardi M. Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations. Blood Advances 2023, 7: 445-457. PMID: 35947128, PMCID: PMC9979716, DOI: 10.1182/bloodadvances.2022008168.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaMalignant CTCL cellsDiverse transcriptomic profilesT cellsSingle-cell RNACTCL cellsDevelopment of CTCLIntegrated transcriptomeT-cell receptor sequencingT cell exhaustion phenotypeCommon antigenic stimulusPeripheral blood CD4Transcriptomic profilesGene expressionT-cell lymphomaIntegrative analysisPotential therapeutic targetProliferation advantageLimited diversityBlood CD4Blood involvementMutation levelsExhaustion phenotypeWorse prognosisAntigenic stimulus
2022
HSV-2 increases replication of HIV in human T cells
Pierce C, Preston-Hurlburt P, Loh L, Steach H, Sidoli S, Zhang F, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 increases replication of HIV in human T cells. The Journal Of Immunology 2022, 208: 182.40-182.40. DOI: 10.4049/jimmunol.208.supp.182.40.Peer-Reviewed Original ResearchCD4 cellsHSV-2HIV reactivationHIV PVLT cellsHerpes simplex virus 2 infectionLncRNA MALAT1Simplex virus 2 infectionHIV-LTR expressionHSV-2 lesionsMALAT1 gene expressionUninfected CD4 cellsFollicular helper cellsHSV-2 infectionCD4 T cellsHIV restriction factorsVirus 2 infectionGlobal HIV epidemicHSV-2 glycoprotein BHIV latent reservoirHuman T cellsInterferon response genesMucosal responsesHSV infectionLatent reservoir
2014
Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice
Mingueneau M, Krishnaswamy S, Spitzer MH, Bendall SC, Stone EL, Hedrick SM, Pe'er D, Mathis D, Nolan GP, Benoist C. Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16466-16471. PMID: 25362052, PMCID: PMC4246343, DOI: 10.1073/pnas.1419337111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Disease Models, AnimalEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGenetic VariationI-kappa B ProteinsImmune ToleranceImmunity, CellularImmunologic Deficiency SyndromesImmunologic MemoryLymph NodesLymphopoiesisMaleMAP Kinase Signaling SystemMass SpectrometryMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMitogen-Activated Protein Kinase 1NF-KappaB Inhibitor alphaPhosphorylationProtein Processing, Post-TranslationalReceptors, Antigen, T-CellSelf ToleranceSingle-Cell AnalysisThymus GlandConceptsT cellsT cell differentiationNOD T cellsERK activationNonobese diabetic (NOD) miceMemory T cellsKO T cellsMass cytometrySingle-cell mass cytometryNOD miceDiabetic miceB6 miceControl C57BL/6Small impairmentMicePrimary deficiencyTCR signalingPhosphorylation levelsLarge defectsTCR triggeringActivationLower ERK activationImpairmentCytometryCellsConditional density-based analysis of T cell signaling in single-cell data
Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GP. Conditional density-based analysis of T cell signaling in single-cell data. Science 2014, 346: 1250689. PMID: 25342659, PMCID: PMC4334155, DOI: 10.1126/science.1250689.Peer-Reviewed Original ResearchConceptsSingle-cell dataMitogen-activated protein kinase ERK2High-dimensional single-cell technologiesProtein kinase ERK2Single-cell technologiesNaïve cellsKinase ERK2Protein speciesCellular circuitsCell variationMolecular circuitsProteinMass cytometryAbundanceCellsCell subtypesComputational approachERK2Computational methodsSpeciesPERKCascadeFunctionT cellsPS6