Experimental limb transplantation, part III: induction of tolerance in the rigorous strain combination of Brown Norway donor to Lewis recipient.
The complete withdrawal of immunosuppressive therapy after hind-limb transplantation across a strong histocompatibility barrier (Brown-Norway to Lewis) included a low-dose combination of FK506, mycophenolate mofetil (MMF), and prednisone. MMF and prednisone were tapered and withdrawn between weeks 2 and 7. From weeks 8 to 24, Group 1 animals (n=23) had FK506 tapered; for those in Group 2 (n=11) the dose of FK506 was not changed. At week 24, FK506 was stopped. The six limb grafts in Group 1 (26%) that achieved the 1-year end-point uneventfully showed chimerism by bone marrow and skin grafting supporting the presence of donor-specific tolerance. Rejection, which was common during tapering of FK506, was reversed by salvage therapy. All limbs were rejected postwithdrawal in Group 2. This study showed that tapering of FK506 combined with salvage therapy may allow long-term survival of some transplanted limbs after complete withdrawal of immunosuppressive therapy despite a complete MHC barrier.
Kanatani
T
T
Department of Orthopedics, Kobe Rosai Hospital, Kobe University, Kobe, Japan. takakokatie@kobeh.rofuku.go.jp
Wright
B
B
Lanzetta
M
M
Molitor
M
M
McCaughan
G W
GW
Bishop
G A
GA
D000818:Animals; D004334:Drug Administration Schedule; D005121:Extremities / Q000637:transplantation*; D006085:Graft Survival / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000276:immunology*
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus