title: Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives.
abstract: Hemopoietic stem cell transplantation (HSCT) is a standard procedure for treatment of malignant and non-malignant hematological diseases. HSCT donors include HLA-identical siblings, matched or mismatched unrelated donors and haploidentical related donors. Graft-versus-host disease (GvHD), mediated by donor alloreactive T-cells in the graft, can be triggered by minor histocompatibility antigens in HLA-identical pairs, by alleles at loci not considered for MUD-matching or by the mismatched haplotype in haplo-HSCT. Therefore, removal of donor T-cells, that contain the alloreactive precursors, is required, but T-cell depletion associates with opportunistic infections and with reduced graft-versus-leukemia effect. Selective T-cell depletion strategies have been introduced, like removal of αβ T-lymphocytes and of naive T-cells, two subsets including the alloreactive precursors, but the ultimate goal is specific removal of alloreactive T-cells. Here we review the different approaches to deplete alloreactive T-cells only and discuss pros and cons, specificity, efficiency and efficacy. Combinations of different methods and innovative approaches are also proposed for depleting specific alloreactive T-cells with high efficiency.
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy; Unit of Immuno-hematology and Transfusion Medicine, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onoforio 4, 00165 Rome, Italy. Electronic address: giuseppina.lipira@opbg.net.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Li Pira
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: stefano.dicecca@opbg.net.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Cecca
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy; Unit of Immuno-hematology and Transfusion Medicine, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onoforio 4, 00165 Rome, Italy. Electronic address: mauro.montanari@opbg.net.
authors.forename: Mauro
authors.initials: M
authors.lastname: Montanari
authors.affiliation: Immunology Area, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onoforio 4, 00165 Rome, Italy. Electronic address: lorenzo.moretta@opbg.net.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Immunology Area, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onoforio 4, 00165 Rome, Italy. Electronic address: fabrizio.manca@opbg.net.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manca
mesh_terms: D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods
keywords: Allodepletion; Alloreactive T-cells; Cell manipulation; Graft-versus-host disease; Hemopoietic stem cell transplantation; T-cell activation