CD8+ CD122+ PD‐1− effector cells promote the development of diabetes in NOD mice

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

关键词: T cells;    insulitis;    autoimmunity;    inflammation;   

DOI  :  10.1189/jlb.3A0613-344RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ItiswellestablishedthatCD4andCD8TcellsarerequiredfortheinitiationofautoimmunediabetesinNODmice.However,differentsubsetsofCD4orCD8cellsmayplaydifferentrolesintheinitiationofinsulitis.Inthisstudy,weevaluatedtheroleofthepreviouslydescribedCD8+CD122+inthisprocess.WefoundthatprediabeticNODmicehaveanalmost50%reductionofCD8+CD122+TcellsintheirsecondarylymphoidorganscomparedwithBL/6orBalb/cmousestrains.ThisreductionisexplainedbythelackoftheregulatoryCD8+CD122+PD‐1+cellpopulationintheNODmice,aswefoundthatallCD8+CD122+TcellsfromprediabeticNODmicelackPD‐1expressionandregulatoryfunction.DepletionofCD8+CD122+PD‐1−cellsthroughinjectionofanti‐CD122mAbinprediabeticfemaleNODmicereducedtheinfiltrationofmononuclearcellsintotheLangerhansisletsanddelayedtheonsetanddecreasedtheincidenceofovertdiabetes.Inaddition,wefoundthattransferofhighlypurifiedandactivatedCD8+CD122+PD‐1−cells,togetherwithdiabetogenicsplenocytesfromNODdonorstoNODSCIDrecipients,acceleratesthediabetesdevelopmentinthesemice.Together,theseresultsdemonstratethatCD8+CD122+PD‐1−TcellsfromNODmiceareeffectorcellsthatareinvolvedinthepathogenesisofautoimmunediabetes...

【 授权许可】

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