Donor specific tolerance for MHC mis-matched murine skin allograft induced by donor bone marrow transplantation with precondition of high dose immunosuppressants / 中华器官移植杂志

ABSTRACT

Objective To establish a non-irradiated precondition strategy for successful donor specific transplantation tolerance induced by bone marrow transplantation which may be introduced to clinical application by a murine model.Methods Male C57BL/6 and female BALB/c mice were used as skin transplant donors and recipients respectively. In all, 11 groups were studied group 1, control mice with skin graft and without any other treatment; group 2, mice receiving only donor bone marrow transplantation (DBMT) before skin transplantation; groups 3～5, mice administrated by only high dose FK506, CsA or CTX respectively and then skin transplantation; groups 6～8, mice receiving DBMT preconditioned by high dose FK506, CsA or CTX respectively and followed by skin transplantation. Both skin and bone marrow donors were male C57BL/6 mice in above 8 groups. Mice in groups 9～11 were treated almost equally to groups 6～8 except that skin grafts were from the third party ICR donors to prove specificity of tolerance. Every group included 6 recipients. Survival time of skin graft was recorded. Macrochimerism were examined by PCR method.Results Neither standard dose DBMT nor high dose immnodepressants alone could prolong skin graft survival, and macrochimerism was not detected, either. But skin graft survival time was significantly prolonged and macrochimerism was also detected in mice of 6～8 groups. Survival time of skin graft from the third party mice was not prolonged. Conclusions Bone marrow transplantation preconditioned with high dose immunosuppressants and without irradiation can induce donor specific transplantation tolerance and prolong murine skin graft survival. It may work through the mechanism of establishment of macrochimerism.