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学科主题: 基础医学
题名:
Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts
作者: Jin, YZ; Zhang, QY; Xie, SS
刊名: TRANSPLANTATION PROCEEDINGS
发表日期: 2003-12-01
DOI: 10.1016/j.transproceed.2003.10.025
卷: 35, 期:8, 页:3156-3159
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]: TOLERANCE ; INDUCTION
英文摘要:

Co-stimulatory blockade combined with donor bone marrow transfusion engenders stable mixed chimerism and robust tolerance to various organ and cell transplants. However, repeated administration of costly agents to block the co-stimulatory pathway and the high doses of donor bone marrow cells (BMCs) used in most protocols are impeding clinical development of this strategy. To circumvent these shortcomings, we developed a plan in which repeated administration of costly agents was replaced by a single injection of adenovirus containing the gene of interest, and the high dose of donor BMCs replaced by a mixture of low-dose donor BMCs and splenocytes (SPLCs). Cardiac allografts from DA(RT- 1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. A cocktail of adenovirus containing CTLA4Ig gene (AdCTLA4Ig), donor BMCs (100 X 10(6)), and SPLCs (50 X 10(6)) was administered to recipients via the portal vein immediately after grafting (n = 6). Treatment with regimens, including AdCTLA4Ig only, AdCTLA4Ig plus donor BMCs, and AdCTLA4Ig plus donor SPLCs, significantly prolonged cardiac allograft survival in recipient rats, while animals that received no treatment or treatment with control adenovirus (AdLacZ) promptly rejected their allografts. Nevertheless, LEW recipients treated with AdCTLA4Ig and the mixture of a low dose of donor BMCs and SPLCs developed stable mixed chimerism, rendering them long-term survivors of cardiac allografts that also accepted skin grafts from the donor but not the third-party strain. We conclude that blockade of CD28-B7 pathway with AdCTLA4Ig plus a mixture of low doses of donor BMCs and SPLCs is a feasible strategy to induce long-term mixed chimerism with a potential application for clinical development.

语种: 英语
WOS记录号: WOS:000187576900085
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57919
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: Peking Univ, Ctr Hlth Sci, Dept Immunol, Beijing 100083, Peoples R China

Recommended Citation:
Jin, YZ,Zhang, QY,Xie, SS. Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts[J]. TRANSPLANTATION PROCEEDINGS,2003,35(8):3156-3159.
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