The Wiskott‐Aldrich syndrome protein regulates CTL cytotoxicity and is required for efficient killing of B cell lymphoma targets

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

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