title: γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes.
abstract: We prospectively assessed functional and phenotypic characteristics of γδ T lymphocytes up to 7 months after HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) depleted of αβ(+) T cells and CD19(+) B cells in 27 children with either malignant or nonmalignant disorders. We demonstrate that (1) γδ T cells are the predominant T-cell population in patients during the first weeks after transplantation, being mainly, albeit not only, derived from cells infused with the graft and expanding in vivo; (2) central-memory cells predominated very early posttransplantation for both Vδ1 and Vδ2 subsets; (3) Vδ1 cells are specifically expanded in patients experiencing cytomegalovirus reactivation and are more cytotoxic compared with those of children who did not experience reactivation; (4) these subsets display a cytotoxic phenotype and degranulate when challenged with primary acute myeloid and lymphoid leukemia blasts; and (5) Vδ2 cells are expanded in vitro after exposure to zoledronic acid (ZOL) and efficiently lyse primary lymphoid and myeloid blasts. This is the first detailed characterization of γδ T cells emerging in peripheral blood of children after CD19(+) B-cell and αβ(+) T-cell-depleted haplo-HSCT. Our results can be instrumental to the development of clinical trials using ZOL for improving γδ T-cell killing capacity against leukemia cells. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
authors.affiliation: Laboratorio di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Irma
authors.initials: I
authors.lastname: Airoldi
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.affiliation: Laboratorio di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Ignazia
authors.initials: I
authors.lastname: Prigione
authors.affiliation: Laboratorio di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Alessia
authors.initials: A
authors.lastname: Zorzoli
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Daria
authors.initials: D
authors.lastname: Pagliara
authors.affiliation: Laboratorio di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Claudia
authors.initials: C
authors.lastname: Cocco
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy;
authors.forename: Raffaella
authors.initials: R
authors.lastname: Meazza
authors.affiliation: Core Facilities, Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loiacono
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Barbarella
authors.initials: B
authors.lastname: Lucarelli
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy;
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.affiliation: Laboratorio di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Giulia
authors.initials: G
authors.lastname: Barbarito
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy;
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, Genova, Italy;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Laboratorio di Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Giannina Gaslini, Genova, Italy;
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: Istituto Giannina Gaslini, Genova, Italy; and.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy; Department of Pediatric Science, University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000293:Adolescent; D018941:Antigens, CD19 / Q000032:analysis*; D001402:B-Lymphocytes / Q000166:cytology*; D015550:Cell Degranulation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000628:therapy*; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000166:cytology / Q000637:transplantation*
chemical_list: D018941:Antigens, CD19; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta