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

[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...

[学科分类] 生理学

[关键词] T cells;insulitis;autoimmunity;inflammation