Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched Bone Marrow Transplantation

被引:23
作者
Davies, Jeffrey K. [1 ,2 ]
Nadler, Lee M. [1 ,2 ]
Guinan, Eva C. [3 ,4 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[4] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA
关键词
VERSUS-HOST-DISEASE; COSTIMULATORY BLOCKADE; ACUTE-LEUKEMIA; DONOR-PROGRAM; HLA; ALLOANTIGEN; INDUCTION; LYMPHOCYTES; ACTIVATION; DEPLETION;
D O I
10.1126/scitranslmed.3000153
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transplantation of hematopoietic stem cells from healthy donors can cure patients with many diseases. Donor T cells can protect against recurrence of infection and disease, but some of these (alloreactive) T cells recognize patient tissues as foreign, causing graft-versus-host disease. Removing T cells from donor grafts before transplantation reduces graft-versus-host disease but increases infection and disease recurrence. Inactivation of alloreactive T cells by inducing tolerance to patient cells (anergization) before transplantation preserves beneficial donor T cell effects while reducing graft-versus-host disease. We show that this approach also results in expansion of regulatory T cells that specifically suppress alloreactive donor T cell responses in the recipient. In addition to reducing graft-versus-host disease, antigen-specific regulatory T cells generated with this strategy could suppress unwanted T cell responses that cause rejection of solid organ transplants and tissue damage in autoimmune disorders.
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页数:9
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