Role of alloreactive KIR2DS1+ NK cells in haploidentical hematopoietic stem cell transplantation

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

关键词: KIR;    CCR7;    GvHD;    HvG;    GvL;   

DOI  :  10.1189/jlb.0311137

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inallo‐HSCT,donor‐derived,″alloreactive″NKcellshavebeenshowntoplayacrucialroleinthetreatmentofacuteleukemia,contributingtoeradicationofleukemicblasts(GvLeffect)andtoclearanceofresidualrecipientDCsandTlymphocytes(thus,preventingGvHDandgraftrejection,respectively).SuchalloreactiveNKcellsdonotexpressCD94/NKG2AbutexpressinhibitoryKIRs,specificforHLAclassIallotypes,presentinthedonorbutlackingintherecipient.ThisreviewisfocusedontheroleoftheactivatingKIR2DS1receptor(specificfortheC2‐epitopeofHLA‐C)inhaplo‐HSCT.RecentdataindicatethatKIR2DS1expressioninHSCdonorsmayrepresentaremarkableadvantageinalloreactiveNKresponses.ThisisaresultofasubstantialincreaseintheNK‐mediatedcapabilitytokill,notonlyrecipientsˈleukemiccellsbutalsoDCsandTcellblasts.ThebeneficialeffectsmediatedbyalloreactiveKIR2DS1+NKcellsmayoccurafterdenovoexpressionofCCR7uponinteractionwithallogeneic,KIRligand‐mismatchedCCR7+cells.Asaconsequence,theycanberedirectedtoLNs,wheretheycanpreventprimingofdonorTcellsandinductionofGvHD.Finally,KIR2DS1expressionmayalsosignificantlyamplifythesizeofthealloreactiveNKcellsubsetbyswitchingasubsetof“notalloreactive”NKcellsintopotentalloreactivecells...

【 授权许可】

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