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

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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.