Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Mauro Di Ianni1,*,
  2. Franca Falzetti2,
  3. Alessandra Carotti2,
  4. Adelmo Terenzi2,
  5. Flora Castellino3,
  6. Elisabetta Bonifacio2,
  7. Beatrice Del Papa2,
  8. Tiziana Zei2,
  9. Roberta Iacucci Ostini2,
  10. Debora Cecchini2,
  11. Teresa Aloisi2,
  12. Katia Perruccio2,
  13. Loredana Ruggeri2,
  14. Chiara Balucani2,
  15. Antonio Pierini2,
  16. Paolo Sportoletti2,
  17. Cynthia Aristei2,
  18. Brunangelo Falini2,
  19. Yair Reisner4,
  20. Andrea Velardi2,
  21. Franco Aversa2, and
  22. Massimo F Martelli2
  1. 1 Chair of Hematology, Department of Internal Medicine and Public Health, University of L'Aquila, Italy;
  2. 2 Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Italy;
  3. 3 Translational Medicine, Novartis Vaccines and Diagnostic, Italy;
  4. 4 Weizmann Institute of Science, Immunology Department, Rehovot, Israel
  1. * Corresponding author; email: mauro.diianni{at}cc.univaq.it

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.