Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
The Wiskott‐Aldrich syndrome protein regulates CTL cytotoxicity and is required for efficient killing of B cell lymphoma targets | |
关键词: cytotoxic T cells; immunodeficiency diseases; tumor immunity; | |
DOI : 10.1189/jlb.0410197 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
WASisaprimaryimmunodeficiencyasaresultofmutationsinthegeneencodingtheWASP,akeyactinregulatorofhematopoieticcells.WhetherkillingdefectsinCD8+CTLscontributetoWAS‐associatedimmunodeficiencyandsusceptibilitytotumordevelopmentremainstobeexplored.CTLlinesfromWASpatients,generatedbyrepeatedstimulationwithSAg‐loadedB‐EBV,displayedreducedproductionofcytokines(IL‐2,IFN‐γ,andTNF‐α)butalmostnormalproliferationuponSAgstimulation.AlthoughWASCTLskilledtargetBcellsinaSAgdose‐dependentmanner,theirefficiencywasreduced,especiallyatalowSAgdose.ThecytotoxicefficiencyofWASCTLswasparticularlyreducedagainsttumoralBcelllines.WASCTLsexpressednormallevelsoflyticmoleculesanddemonstratedefficientexocytosisupontargetcellencounter.However,thelyticgranulesappearednottofullypolarizetowardthecenteroftheCTL/tumortargetcellcontactarea.Importantly,theuseofagenetherapylentiviralvectorwassufficienttorestoreefficientcytotoxicactivity.OurstudysuggeststhatCTLdysfunctioncontributestothedevelopmentofhematologicalmalignanciesinWASpatients...
【 授权许可】
CC BY
【 预 览 】
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