title: Role of alloreactive KIR2DS1(+) NK cells in haploidentical hematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Simona
authors.initials: S
authors.lastname: Carlomagno
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesce
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Simona
authors.initials: S
authors.lastname: Sivori
mesh_terms: D000208:Acute Disease; D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology* / Q000628:therapy*; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000276:immunology; D054340:Receptors, KIR / Q000096:biosynthesis / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: C515370:CCR7 protein, human; D015395:Histocompatibility Antigens Class I; C496212:KIR2DS1 protein, human; D054400:Receptors, CCR7; D054340:Receptors, KIR