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

• Published in: Blood Vol. 117; no. 14; pp. 3921 - 3928
• Main Authors: Di Ianni, Mauro, Falzetti, Franca, Carotti, Alessandra, Terenzi, Adelmo, Castellino, Flora, Bonifacio, Elisabetta, Del Papa, Beatrice, Zei, Tiziana, Ostini, Roberta Iacucci, Cecchini, Debora, Aloisi, Teresa, Perruccio, Katia, Ruggeri, Loredana, Balucani, Chiara, Pierini, Antonio, Sportoletti, Paolo, Aristei, Cynthia, Falini, Brunangelo, Reisner, Yair, Velardi, Andrea, Aversa, Franco, Martelli, Massimo F.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 07.04.2011; Americain Society of Hematology
• Subjects: Adult; Biological and medical sciences; Female; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Hematologic and hematopoietic diseases; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Histocompatibility - immunology; Histocompatibility Testing; Humans; Immune System - immunology; Immune System - physiology; Male; Medical sciences; Middle Aged; Recurrence; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - physiology; T-Lymphocytes, Regulatory - transplantation; Transplantation Conditioning - methods; Transplantation Immunology - physiology; Transplantation, Homologous; Young Adult; Prevention; Immunopathology; Graft versus host disease; HLA-System; Haploidentical graft; Hematology; Stem cell; Major histocompatibility system; Hematopoietic cell; Immune reconstitution
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-10-311894

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 coinfused 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.