Interferon‐α inhibits CD4 T cell responses to interleukin‐7 and interleukin‐2 and selectively interferes with Akt signaling

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

关键词: homeostatic proliferation;    cytokines;   

DOI  :  10.1189/jlb.4A0714-345RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PersistenttypeIIFNproductionoccursduringchronicviralinfections,suchasHIVdisease.AstypeIIFNshaveantiproliferativeactivity,itispossiblethatchronicexposuretothesecytokinescouldadverselyaffectTcellhomeostasis.WeinvestigatedthecapacityofIFN‐αtoimpairTcellproliferationinducedbythehomeostaticcytokine,IL‐7,oranothercommonγ‐chaincytokine,IL‐2,incellsfromhealthyhumandonors.WefoundthatIL‐7‐orIL‐2‐inducedproliferationofCD4+TcellswaspartiallyinhibitedinthepresenceofIFN‐α.TheCD4+TcellsthatwereexposedtoIFN‐αalsodisplayedattenuatedinductionofIL‐2andCD40LfollowingTCRstimulation.AnalysesofsignalingpathwaysindicatedthatIL‐7andIL‐2inducedadelayedandsustainedP‐AktsignalthatlastedforseveraldaysandwaspartiallyinhibitedbyIFN‐α.Incontrast,IL‐7‐inducedP‐STAT5wasnotaffectedbyIFN‐α.Furthermore,IFN‐αhadnodetectableeffectonP‐AktthatwasinducedbythechemokineSDF‐1.BothinhibitorsofP‐AktandP‐STAT5blockedIL‐7‐inducedTcellproliferation,confirmingthatbothsignalingpathwaysareimportantforIL‐7‐inducedTcellproliferation.TheseresultsdemonstratethatIFN‐αcanselectivelyinhibitcytokine‐inducedP‐AktasapotentialmechanismtodisrupthomeostasisofTlymphocytes...

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