title: Haploidentical Haematopoietic Stem Cell Transplantation: Role of NK Cells and Effect of Cytomegalovirus Infections.
abstract: Natural killer cells play an important role in the immune responses against cancer and viral infections. In addition, NK cells have been shown to exert a key role in haploidentical hematopoietic stem cell (HSC) transplantation for the therapy of high-risk leukemias. The anti-leukemia effect is mostly related to the presence of "alloreactive" NK cells, i.e., mature KIR(+) NK cells that express inhibitory KIR mismatched with HLA class I (KIR-L) of the patient. In addition, an important role is played by certain activating KIR (primarily, but not only, KIR2DS1) upon interaction with their HLA class I ligand (C2 alleles). In general, the presence of activating KIR correlates with a better prognosis. Beside the infusion of "pure" CD34(+) cells, a novel protocol has been recently developed in which depletion of αβ T cells and CD19(+) B cells makes it possible to infuse into the patient, together with donor CD34(+) HSCs, important effector cells including mature PB NK cells and γδ T cells. Recent studies revealed that cytomegalovirus (CMV) infection/reactivation may induce rapid NK cell maturation and greatly influence the NK receptor repertoire. The remarkable expansion of a subset expressing the activating receptor NKG2C, together with a more efficient virus-specific effector response after rechallenge with CMV (i.e., antigen specificity), and the longevity of the expanded population are all features consistent with an adaptive type of response and support the notion of a memory-like activity of NK cells.
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione Istologia and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Via G.B. Marsano 10, 16132, Genoa, Italy. mariella.dellachiesa@unige.it.
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.affiliation: IRCCS Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione Istologia and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Via G.B. Marsano 10, 16132, Genoa, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Muccio
authors.affiliation: Department of Pediatric Hematology/Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.affiliation: Department of Medicine, University of Verona and Ospedale Sacro Cuore Negrar (VR), Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Moretta
authors.affiliation: Department of Pediatric Hematology/Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.|Department of Pediatrics, University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione Istologia and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Via G.B. Marsano 10, 16132, Genoa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
mesh_terms: D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D014184:Transplantation, Homologous