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

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，排斥反应和GVHD的免疫机制尚不清楚。采用静脉-袖带技术对Brown-Norway大鼠进行完全同种异体原位小肠移植。记录FK506给药后的排斥反应、GVHD和宿主生存时间。测定宿主和移植物的肝脏、脾脏和肠系膜淋巴结（MLN）的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。给予FK506 0.5mg/kg/天剂量的大鼠出现暂时性GVHD，无排斥迹象，存活超过100天。给予FK506 1.0mg/kg/d的大鼠未发生GVHD。然而，其中一些人出现了慢性排斥反应，并在84天内死亡。免疫学分析表明，NK和CTL活性高的大鼠发生急性排斥反应，NK活性大于CTL活性时发生暂时性GVHD。这些活性在肝脏和移植物MLN中更大。虽然FK506同时抑制NK和CTL活性，但不同剂量的FK506产生不同的免疫抑制作用。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的活性。

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.