dc.description.abstract | The purpose of this study is to establish a simple surgical model of limb
allotransplantation in order to study the nature of graft versus host disease. Two
transplantation models were developed, which included, Osteo-myo-cutaneous (OMC)
transplant model and the traditional full-limb transplant model. Brown Norway(BN)
to Lewis(LEW) rats combination was used in the study. Leflunomide at the dose of
10mg/kg with cyclosporine (short term:30 days, Long term: 60 days) or FK506 (lowdose:
0.1 mg/kg, high-dose: 0.5 mg/kg) /kg) were given as immunosuppresants after
transplantation. After stoppING the immunosuppression agents, clinical sign of
GVHD or rejection of the grafts were observed and histologically examined using
ED1 monoclonal antibodies in order to investigate the macrophage activity during
GVHD. Finally, we compared the GVHD after limb allotransplantation with the
GVHD after clinical bone marrow transplantation and P to Fl animal model in the
references. As a result, only the traditional limb transplantation model developed
GVHD, two of six rats showed clinical signs including sudden weight loss, poor spirit,
ocular and nasal discharge, and dyspnea. Lung and lymphoid tissues (thymus and
mesenteric lymph nodes) were the major target organs in pathology, which was
different from GVHD after BMT. However, some rats in the OMC model, with high
dose of FK506 showed the histological but not clinical evidence of GVHD. In the
observation of graft rejection, the traditional limb grafts were more easily rejected
than the OMC model. And high dose FK506 combined with leflunomide gave more
protection than other immunosupression protocols. The macrophage activity increased
during GVHD,which is similar to the changes during GVHD after BMT. | en |