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学科主题: 临床医学
题名:
A substantial level of donor hematopoietic chimerism is required to protect donor-specific islet grafts in diabetic nod mice.
作者: Guo, Z; Wu, T; Sozen, H; Pan, Y; Heuss, N; Kalscheuer, H; Sutherland, DER; Blazar, BR; Hering, BJ
刊名: TRANSPLANTATION
发表日期: 2003-04-15
DOI: 10.1097/01.TP.0000057832.92231.F5
卷: 75, 期:7, 页:909-915
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Surgery ; Transplantation
研究领域[WOS]: Immunology ; Surgery ; Transplantation
关键词[WOS]: REGULATORY T-CELLS ; BONE-MARROW TRANSPLANTATION ; SKIN ALLOGRAFT TOLERANCE ; ALLOGENEIC CHIMERISM ; MIXED CHIMERISM ; AUTOIMMUNE-DISEASES ; INDUCTION ; IMMUNOSUPPRESSION ; MYELOABLATION ; THYMOCYTES
英文摘要:

Background. Mixed chimerism can induce tolerance to alloantigens and restore self-tolerance to autoantigens, thereby permitting islet transplantation. However, the minimal level of donor chimerism that is required to prevent islet allograft rejection and recurrence of autoimmune diabetes has not been established.

Methods. We investigated whether allogeneic Balb/c donor chimerism can be induced in C57BL/6 mice, in prediabetic NOD mice, and in diabetic NOD mice after transplantation of a modest dose of bone marrow by using purine nucleoside analogue, fludarabine phosphate and cyclophosphamide conditioning therapy, followed by short-term anti-CD40 ligand monoclonal antibody and rapamycin posttransplant treatment. We also investigated whether the induced donor chimerism is sufficient to prevent the onset of diabetes in prediabetic NOD mice and protect donor islet grafts in diabetic NOD mice.

Results. Allogeneic donor chimerism could be induced under the authors′ approach that is nonmyeloablative and radiation-free. Diabetes onset was prevented in chimeric prediabetic NOD mice. The induction of mixed chimerism protected donor-specific islet grafts in diabetic NOD mice. At 60 days after islet transplantation, all donor Balb/c islet grafts survived in diabetic NOD mice whose level of donor-derived lymphocytes was higher than 30% at the time of islet transplantation (n=8). In contrast, Balb/c islet grafts were rejected in five of seven diabetic NOD mice whose level was lower than 30%.

Conclusions. Our data demonstrate that a donor lymphocyte chimerism (>30%) at the time of islet transplantation is required to protect donor-specific islet grafts, and indicate that a strictly non-irradiation-based protocol can be used to achieve this goal.

语种: 英语
WOS记录号: WOS:000182338500001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58560
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, Hosp 1st, Dept Surg, Beijing, Peoples R China
2.Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
3.Univ Minnesota, Diabet Inst Immunol & Transplantat, Minneapolis, MN 55455 USA
4.Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA
5.Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA

Recommended Citation:
Guo, Z,Wu, T,Sozen, H,et al. A substantial level of donor hematopoietic chimerism is required to protect donor-specific islet grafts in diabetic nod mice.[J]. TRANSPLANTATION,2003,75(7):909-915.
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