HMBPP‐deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells

[摘要] Whereasinfectionorimmunizationofhumans/primateswithmicrobescoproducingHMBPP/IPPcanremarkablyactivateVγ2Vδ2Tcells,invivostudieshavenotbeendonetodissectHMBPP‐andIPP‐drivenexpansion,pulmonarytrafficking,effectorfunctions,andmemorypolarizationofVγ2Vδ2Tcells.Wedefinethesephosphoantigen‐hostinterplaysbycomparativeimmunizationsofmacaqueswiththeHMBPP/IPP‐coproducingListeriaΔactAprfA*andHMBPP‐deficientListeriaΔactAΔgcpEprfA*mutant.TheHMBPP‐deficientΔgcpEmutantshowslowerabilitytoexpandVγ2Vδ2TcellsinvitrothantheparentalHMBPP‐producingstrainbutdisplayscomparablyattenuatedinfectivityorimmunogenicity.RespiratoryimmunizationofmacaqueswiththeHMBPP‐deficientmutantelicitslowerpulmonaryandsystemicresponsesofVγ2Vδ2TcellscomparedwiththeHMBPP‐producingvaccinestrain.Interestingly,HMBPP‐deficientmutantreimmunizationorboostingelicitsenhancedresponsesofVγ2Vδ2Tcells,butthemagnitudeislowerthanthatbyHMBPP‐producinglisteria.HMBPP‐deficientlisteriadifferentiatedfewerVγ2Vδ2TeffectorcellscapableofcoproducingIFN‐γandTNF‐αandinhibitingintracellularlisteriathanHMBPP‐producinglisteria.Furthermore,HMBPPdeficiencyinlisterialimmunizationinfluencesmemorypolarizationofVγ2Vδ2Tcells.Thus,bothHMBPPandIPPproductioninlisterialimmunizationorinfectionelicitsystemic/pulmonaryresponsesanddifferentiationofVγ2Vδ2Tcells,butaroleforHMBPPismoredominant.Findingsmayhelpdeviseimmuneintervention...

[学科分类] 生理学

[关键词] T cells;antigen;cell activation;memory response;lung