CD8 down‐regulation and functional impairment of SIV‐specific cytotoxic T lymphocytes in lymphoid and mucosal tissues during SIV infection

[摘要] Functionalimpairmentofvirus‐specificTcellsisahallmarkofHIV/SIVinfection,buttheunderlyingmechanismsofthisdysfunctionarenotwellunderstood.Toaddressthis,wesimultaneouslyanalyzedtheexpressionandintensityofCD8andinhibitoryPD‐1onCTLinbloodandlymphoidtissuesinSIV‐infectedrhesusmacaques.Theintensity(meanchannelfluorescence)ofCD8expressionwastransientlydown‐regulatedinearlySIVinfection(10–14dpi),despiteanincreaseinCD8+Tcellproliferation.Inchronicinfection,CD8expressionwasmaintainedatlowlevelsonCD8+Tcellsinalltissues.Interestingly,Gag‐specificCTLswereclearlydividedintoCD8high‐andCD8low‐expressingpopulationsinSIV‐infectedmacaques,andCD8lowGag‐specificcellsincreasedwithdiseaseprogression,especiallyinlymphoidtissueswhencomparedwithperipheralbloodorinGag‐vaccinatedcontrols.Moreover,theCD8lowCTLpopulationsecretedlowerlevelsofcytokinesuponSIVantigenstimulationandexhibitedlowerproliferativecapacityduringinfectioncomparedwiththeCD8highCTLpopulation.Meanwhile,intensityofPD‐1expressiononGag‐specificCTLinchronicinfectionwassignificantlyhigherthaninacuteSIVinfection,althoughthefrequenciesofPD‐1+Gag‐specificcellsweresimilarinacuteandchronicstages.Insummary,down‐regulationofCD8expressionandhigherexpressionofPD‐1onSIV‐specificCTLscouldcoordinatelyattenuateSIV‐specificCTLresponsesandtheirabilitytorecognizevirus‐infectedtargetcells,especiallyinlymphoidtissues,resultinginfailuretocontainviremia,andcontinuedpersistenceandreplicationofHIVinlymphoidtissuereservoirs...

[学科分类] 生理学

[关键词] CD8+ T cell;CTL;HIV;intestine;immunology