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

Mauro Di Ianni, Franca Falzetti, Alessandra Carotti, Adelmo Terenzi, Flora Castellino, Elisabetta Bonifacio, Beatrice Del Papa, Tiziana Zei, Roberta Iacucci Ostini, Debora Cecchini, Teresa Aloisi, Katia Perruccio, Loredana Ruggeri, Chiara Balucani, Antonio Pierini, Paolo Sportoletti, Cynthia Aristei, Brunangelo Falini, Yair Reisner, Andrea Velardi, Franco Aversa, Massimo F Martelli

Abstract

Hastening post-transplant immune reconstitution is a key challenge in HLA-haploidentical haematopoietic stem cell transplantation (HSCT). In experimental models of mismatched HSCT T regulatory cells (Tregs), when coinfused with conventional T cells (Tcons), favoured post-transplant immune reconstitution and prevented lethal GvHD. The present study evaluated the impact of early infusion of Tregs, followed by Tcons, on GvHD prevention and immunological reconstitution, in 28 patients with high risk haematological 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 post-transplant immunosuppression, promoted lymphoid reconstitution, improved immunity to opportunistic pathogens and did not weaken the Graft vs Leukaemia effect. This study provides evidence that Tregs are a conserved mechanism in human beings.

  • Submitted October 6, 2010.
  • Accepted December 14, 2010.