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Immunosuppressive mechanism by FK506 following small bowel trasplantation in rats-analysing for immunologic factors-

大鼠小肠移植后FK506的免疫抑制机制-免疫因素分析-

基本信息

批准号：
08671398
负责人：
NAKAI Takuya
金额：
$ 1.28万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671398/
关键词：
rat small bowel transplantation FK506 rejection GVHD 小腸移植ラット小腸移植 Chimerism HVGD

项目摘要

Rejection and graft-versus-host disease (GVHD) are observed following fully allogeneic small bowel transplantation. However, the immunologic mechanisms responsible for rejection and GVHD are still unclear.Fully allogeneic orthotopic small bowel transplantation from Brown-Norway to Lewis rats were performed using a venous-cuff technique. Signs of rejection and GVHD and host survial time following FK506 administration were recorded. Natural killer (NK) cell activity and CTL (cytotoxic T lymphocyte) activity in the liver, spleen and mesenteric lymph node (MLN) of the host and MLN of the graft were measured.Rats not given FK506 developed acute rejection. Rats given FK506 at a dose of 0.5mg/kg/day developed temporary GVHD without evidence of rejection and survived more than 100 days. Rats given 1.0mg/kg/day of FK506 did not develop GVHD.However, some of them developed chronic rejection and died within 84 days. Immunologic analysis demonstrated that acute rejection occurred in rats that showed high levels of NK and CTL activities, and that temporary GVHD occurred when the NK activity was greater than the CTL activity. These activities were greater in the liver and the graft MLN.Although FK506 suppresses both NK and CTL activities, different doses of the agent result in different immunosuppressive effects. GVHD and rejection after fully allogeneic small bowel transplantation occur depending on NK and CTL activities.

完全同种异体小肠移植后观察到排斥反应和移植物抗宿主病（GVHD）。然而，引起排斥反应和GVHD的免疫机制仍不清楚。使用静脉套囊技术对Brown-Norway大鼠进行全同种异体原位小肠移植。记录 FK506 给药后的排斥反应和 GVHD 以及宿主存活时间。测量宿主的肝脏、脾脏和肠系膜淋巴结(MLN)以及移植物的MLN中的自然杀伤(NK)细胞活性和CTL(细胞毒性T淋巴细胞)活性。未给予FK506的大鼠出现急性排斥反应。以 0.5 毫克/公斤/天的剂量给予 FK506 的大鼠出现暂时性 GVHD，没有排斥反应的证据，并存活了 100 多天。给予1.0mg/kg/天FK506的大鼠没有出现GVHD。然而，其中一些大鼠出现慢性排斥反应并在84天内死亡。免疫学分析表明，NK和CTL活性高的大鼠会发生急性排斥反应，当NK活性大于CTL活性时，会发生暂时性GVHD。这些活性在肝脏和移植物 MLN 中更大。尽管 FK506 抑制 NK 和 CTL 活性，但不同剂量的药物会导致不同的免疫抑制效果。完全同种异体小肠移植后 GVHD 和排斥反应的发生取决于 NK 和 CTL 活性。