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学科主题: 临床医学
题名:
Increasing donor chimerism and inducing tolerance to islet allografts by post-transplant donor lymphocyte infusion
作者: Liu, BL; Hao, JQ; Pan, YS; Luo, B; Westgard, B; Heremans, Y; Sutherland, DER; Hering, BJ; Guo, ZG
关键词: islet transplantation ; tolerance ; type 1 diabetes ; autoimmunity ; chimerism ; bone marrow transplantation
刊名: AMERICAN JOURNAL OF TRANSPLANTATION
发表日期: 2006-05-01
DOI: 10.1111/j.1600-6143.2006.01283.x
卷: 6, 期:5, 页:933-946
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Surgery ; Transplantation
研究领域[WOS]: Surgery ; Transplantation
关键词[WOS]: REGULATORY T-CELLS ; NONOBESE DIABETIC MICE ; BONE-MARROW-TRANSPLANTATION ; IMMUNOLOGICAL SELF-TOLERANCE ; VERSUS-HOST-DISEASE ; NOD MICE ; HEMATOPOIETIC CHIMERISM ; ADOPTIVE IMMUNOTHERAPY ; CONDITIONING THERAPY ; ALLOGENEIC CHIMERAS
英文摘要:

Inducing donor chimerism is the most consistently successful approach to achieve transplant tolerance. We found that a low level of donor chimerism, which was induced by a relatively non-toxic approach, induced donor-specific tolerance to islet allografts in chemically induced diabetic mice. However, a similar level of donor chimerism could not protect donor islet allografts in non-obese diabetic (NOD) mice that spontaneously developed autoimmune diabetes. Rejection of donor islet allografts in diabetic NOD mice with a low level of donor chimerism was mediated by recurrent autoimmunity. We used post-transplant donor lymphocyte infusion (DLI) to increase donor chimerism and to induce tolerance to islet allografts. DLI significantly increased donor chimerism and promoted donor-specific tolerance to islet allografts in diabetic NOD mice. Self-tolerance to islet autoantigens was restored and restoring self-tolerance is mediated by immunoregulation. Thus, our data showed that adoptive immunotherapy with post-transplant DLI after establishing a low level of donor chimerism as a platform enhances donor chimerism, induces donor-specific tolerance to islet allografts and restores self-tolerance in the setting of autoimmune diabetes. Our data also showed that central tolerance is not sufficient to induce tolerance and peripheral tolerance through immunoregulation for restoring self-tolerance is required in the setting of autoimmune diabetes.

语种: 英语
WOS记录号: WOS:000236860700010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58270
Appears in Collections:北京大学第一临床医学院_普通外科_期刊论文

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作者单位: 1.Beijing Univ, Dept Surg, Hosp 1, Beijing 100871, Peoples R China
2.Univ Alberta, Dept Surg, Edmonton, AB, Canada
3.Univ Minnesota, Inst Immunol & Transplantat, Dept Surg & Diabet, Minneapolis, MN 55455 USA
4.China Med Univ, Second Affiliated Hosp, Dept Surg, Shenyang, Liaoning, Peoples R China
5.Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA

Recommended Citation:
Liu, BL,Hao, JQ,Pan, YS,et al. Increasing donor chimerism and inducing tolerance to islet allografts by post-transplant donor lymphocyte infusion[J]. AMERICAN JOURNAL OF TRANSPLANTATION,2006,6(5):933-946.
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