IL‐23R and TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells expressing high levels of cytotoxic mediators and producing IFN‐γ and IL‐17

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

关键词: newborn;    human;    γ;    δ;    IL‐;    23;   

DOI  :  10.1189/jlb.0910501

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theimmunesysteminearlylifeisregardedasimmature.However,theIL‐12familymemberIL‐23ishighlyproduceduponTLRstimulationbyneonatalDCs.HumanadultVγ9Vδ2TcellscanbestimulatedspecificallyviatheirTCRbyphosphoantigens(asthepathogen‐derivedHMB‐PP)oragentsandinfectionsthatleadtotheirendogenousaccumulation(astheaminobisphosphonatezoledronate).AsincreasingevidenceindicatesthatγδTcellsareespeciallyimportantinearlylife,weinvestigatedtheeffectofIL‐23onneonatalVγ9Vδ2TcellsstimulatedviatheirTCR.ZoledronateinducedclearproliferationandIFN‐γproductioninneonatalVγ9Vδ2Tcells.Incontrast,HMB‐PPdidnotelicitadistinctresponseunlessathighconcentrations.AdditionofIL‐23tozoledronateenhancedtheexpressionofIFN‐γandgeneratedadistinct,IFN‐γ‐negative,neonatalVγ9Vδ2TcellpopulationproducingIL‐17.Furthermore,IL‐23significantlyenhancedtheexpressionofarangeofcytotoxicmediators(perforin,granzymes,granulysin).AlthoughthecostimulatoryeffectofIL‐23onIFN‐γandcytotoxicmediatorswasalsoobservedwithinadultVγ9Vδ2Tcells,theinductionofanIL‐17+IFN‐γ–subsetwasuniquetoneonatalVγ9Vδ2Tcells.Inconclusion,neonatalDC‐derivedIL‐23combinedwithspecificTCRsignalingdrivesthegenerationofneonatalVγ9Vδ2TcellsequippedwitharangeofcytotoxicmediatorsanddistinctsubpopulationsproducingIFN‐γandIL‐17...

【 授权许可】

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