Identification of a bone marrow‐derived CD8αα+ dendritic cell‐like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis

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

关键词: autoimmunity;    apoptosis;    tolerance;    kidney;   

DOI  :  10.1189/jlb.0310133

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

DCsplaycriticalrolesinpromotionofautoimmunityorimmunetoleranceaspotentAPCs.Inouranti‐GBMGNmodel,WKYratsdevelopsevereTcell‐mediatedglomerularinflammationfollowedbyfibrosis.ADC‐likecellpopulation(CD8αα+CD11c+MHC‐II+ED1–)wasidentifiedintheinflamedglomeruli.ChimeraexperimentsdemonstratedthattheCD8αα+cellswerederivedfromBM.TheCD8αα+cellsinfiltratedglomeruliatalatestage(Days28–35),coincidentwitharapiddeclineinglomerularinflammationbeforefibrosis.TheCD8αα+cellsisolatedfrominflamedglomeruliwereabletomigraterapidlyfromthebloodstreamintoinflamedglomerulibutnotintonormalglomeruli,suggestingthatthemigrationwastriggeredbylocalinflammation.Despitehigh‐levelexpressionofsurfaceandcellularMHCclassIImolecules,invitroexperimentsshowedthatthisCD8αα+DC‐likecellinducedapoptosisbutnotproliferationinantigen‐specificCD4+TcellsfromTcelllinesorfreshlyisolatedfromlymphnodes;theywerenotabletodosointheabsenceofantigens,suggestinginductionofapoptosiswasantigen‐specific.Furthermore,apoptoticTcellsweredetectedinalargenumberintheglomeruliatDay32,coincidentwiththeinfiltrationofthecellsintoglomeruli,suggestingthatthecellsmayalsoinduceTcellapoptosisinvivo.ApotentialroleofthisCD8αα+DC‐likepopulationinperipheralimmunetoleranceand/orterminationofautoimmuneinflammationwasdiscussed...

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