Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation

Mauro Di Ianni(University of L'Aquila), Franca Falzetti(University of Perugia), Alessandra Carotti(University of Perugia), Adelmo Terenzi(University of Perugia), Flora Castellino(Novartis (Italy)), Elisabetta Bonifacio(University of Perugia), Beatrice Del Papa(University of Perugia), Tiziana Zei(University of Perugia), Roberta Iacucci Ostini(University of Perugia), Debora Cecchini(University of Perugia), Teresa Aloisi(University of Perugia), Katia Perruccio(University of Perugia), Loredana Ruggeri(University of Perugia), Chiara Balucani(University of Perugia), Antonio Pierini(University of Perugia), Paolo Sportoletti(University of Perugia), Cynthia Aristei(University of Perugia), Brunangelo Falini(University of Perugia), Yaīr Reisner(Weizmann Institute of Science), Andrea Velardi(University of Perugia), Franco Aversa(University of Perugia), Massimo F. Martelli(University of Perugia)
Blood
February 3, 2011
10.1182/blood-2010-10-311894
Cited by 1,047Open Access
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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.

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