Depletion of CD4+ CD25+ regulatory T cells confers susceptibility to experimental autoimmune encephalomyelitis (EAE) in GM‐CSF‐deficient Csf2−/− mice

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

关键词: multiple sclerosis;    FOXP3+ T cells;    tolerance;    neuroimmunology;   

DOI  :  10.1189/jlb.3A0815-359R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PreviousstudiesestablishedthatGM‐CSF‐deficient(Csf2‐deficient)miceexhibitprofoundresistancetoexperimentalautoimmuneencephalomyelitis.ThisstudyaddressedwhethertheresistanceofCsf2‐deficientmicewasaresultofarequirementforGM‐CSFincontrollingthefunctionalbalancebetweeneffectorandregulatoryTcellsubsetsduringexperimentalautoimmuneencephalomyelitis.Themainobservationwasthattreatmentwiththeanti‐CD25mAbPC61renderedCsf2‐deficientmicefullysusceptibletosevere,chronicexperimentalautoimmuneencephalomyelitis,withdiseaseincidencesandseveritiesequivalenttothatofC57BL/6mice.WhenbothdonorsandrecipientsweretreatedwithPC61inapassivemodelofexperimentalautoimmuneencephalomyelitis,adoptivetransferofmyelin‐specificCsf2‐deficientTcellsintoCsf2‐deficientrecipientsresultedinanonresolvingchroniccourseofsevereparalyticexperimentalautoimmuneencephalomyelitis.TheperipheralCsf2‐deficientTcellrepertoirewasmarkedbyelevatedCD3+TcellfrequenciesthatreflectedsubstantialaccumulationsofnaïveCD44null‐lowCD4+andCD8+TcellsbutessentiallynormalfrequenciesofCD4+CD25+forkheadboxP3+TcellsamongtheCD3+Tcellpool.ThesefindingssuggestedthatCsf2‐deficientmicehadsecondarydeficienciesinperipheralTcellsensitizationtoenvironmentalantigens.Inaccordance,myelinoligodendrocyteglycoprotein35–55/CFA‐sensitizedCsf2‐deficientmiceexhibiteddeficientperipheralsensitizationtomyelinoligodendrocyteglycoprotein,whereaspretreatmentofCsf2‐deficientmicewithPC61enabledtherobustinductionofmyelinoligodendrocyteglycoprotein‐specificTcellresponsesinthedraininglymphatics.Inconclusion,theexperimentalautoimmuneencephalomyelitisresistanceofCsf2‐deficientmice,atleastinpart,reflectsadeficientinductionofeffectorTcellfunctionthatcannotsurmountnormalregulatoryTcellbarriers.Experimentalautoimmuneencephalomyelitiseffectorresponses,however,areunleashedupondepletionofregulatoryCD25+Tcells...

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