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

Journal of Leukocyte Biology

Emanuela Marcenaro¹  Simona Carlomagno¹  Mariella Della Chiesa¹  Alessandro Moretta , and¹  Silvia Pesce¹  Simona Sivori ¹ 

[1] Dipartimento di Medicina Sperimentale and  Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy

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 】

In allo-HSCT, donor-derived, ″alloreactive″ NK cells have been shown to play a crucial role in the treatment of acute leukemia, contributing to eradication of leukemic blasts (GvL effect) and to clearance of residual recipient DCs and T lymphocytes (thus, preventing GvHD and graft rejection, respectively). Such alloreactive NK cells do not express CD94/NKG2A but express inhibitory KIRs, specific for HLA class I allotypes, present in the donor but lacking in the recipient. This review is focused on the role of the activating KIR2DS1 receptor (specific for the C2-epitope of HLA-C) in haplo-HSCT. Recent data indicate that KIR2DS1 expression in HSC donors may represent a remarkable advantage in alloreactive NK responses. This is a result of a substantial increase in the NK-mediated capability to kill, not only recipients' leukemic cells but also DCs and T cell blasts. The beneficial effects mediated by alloreactive KIR2DS1+ NK cells may occur after de novo expression of CCR7 upon interaction with allogeneic, KIR ligand-mismatched CCR7+ cells. As a consequence, they can be redirected to LNs, where they can prevent priming of donor T cells and induction of GvHD. Finally, KIR2DS1 expression may also significantly amplify the size of the alloreactive NK cell subset by switching a subset of “not alloreactive” NK cells into potent alloreactive cells.

【 授权许可】

Unknown