title: Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation.
abstract: Hastening posttransplantation immune reconstitution is a key challenge in human leukocyte antigen (HLA)-haploidentical hematopoietic stem-cell transplantation (HSCT). In experimental models of mismatched HSCT, T-regulatory cells (Tregs) when co-infused with conventional T cells (Tcons) favored posttransplantation immune reconstitution and prevented lethal graft-versus-host disease (GVHD). In the present study, we evaluated the impact of early infusion of Tregs, followed by Tcons, on GVHD prevention and immunologic reconstitution in 28 patients with high-risk hematologic malignancies who underwent HLA-haploidentical HSCT. We show for the first time in humans that adoptive transfer of Tregs prevented GVHD in the absence of any posttransplantation immunosuppression, promoted lymphoid reconstitution, improved immunity to opportunistic pathogens, and did not weaken the graft-versus-leukemia effect. This study provides evidence that Tregs are a conserved mechanism in humans.
authors.affiliation: Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy. mauro.diianni@cc.univaq.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Ianni
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carotti
authors.forename: Adelmo
authors.initials: A
authors.lastname: Terenzi
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Beatrice
authors.initials: B
authors.lastname: Del Papa
authors.forename: Tiziana
authors.initials: T
authors.lastname: Zei
authors.forename: Roberta Iacucci
authors.initials: RI
authors.lastname: Ostini
authors.forename: Debora
authors.initials: D
authors.lastname: Cecchini
authors.forename: Teresa
authors.initials: T
authors.lastname: Aloisi
authors.forename: Katia
authors.initials: K
authors.lastname: Perruccio
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Chiara
authors.initials: C
authors.lastname: Balucani
authors.forename: Antonio
authors.initials: A
authors.lastname: Pierini
authors.forename: Paolo
authors.initials: P
authors.lastname: Sportoletti
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aristei
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
mesh_terms: D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006648:Histocompatibility / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology* / Q000637:transplantation; D019172:Transplantation Conditioning / Q000379:methods; D014181:Transplantation Immunology / Q000502:physiology; D014184:Transplantation, Homologous; D055815:Young Adult