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

被引:383
作者
Di Ianni, Mauro [1 ,2 ]
Falzetti, Franca [2 ]
Carotti, Alessandra [2 ]
Terenzi, Adelmo [2 ]
Castellino, Flora
Bonifacio, Elisabetta [2 ]
Del Papa, Beatrice [2 ]
Zei, Tiziana [2 ]
Ostini, Roberta Iacucci [2 ]
Cecchini, Debora [2 ]
Aloisi, Teresa [2 ]
Perruccio, Katia [2 ]
Ruggeri, Loredana [2 ]
Balucani, Chiara [2 ]
Pierini, Antonio [2 ]
Sportoletti, Paolo [2 ]
Aristei, Cynthia [2 ]
Falini, Brunangelo [2 ]
Reisner, Yair [3 ]
Velardi, Andrea [2 ]
Aversa, Franco [2 ]
Martelli, Massimo F. [2 ]
机构
[1] Univ Aquila, Chair Hematol, Dept Internal Med & Publ Hlth, I-67100 Laquila, Italy
[2] Univ Perugia, Dept Clin & Expt Med, Hematol & Clin Immunol Sect, I-06100 Perugia, Italy
[3] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
关键词
VERSUS-HOST-DISEASE; REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; ADOPTIVE IMMUNOTHERAPY; ACUTE-LEUKEMIA; HIGH-RISK; MEGADOSE; BARRIERS; DONORS;
D O I
10.1182/blood-2010-10-311894
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood. 2011; 117(14):3921-3928)
引用
收藏
页码:3921 / 3928
页数:8
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