J Korean Soc Microsurg.  2009 May;18(1):9-15.

Long-Term Acceptance of Fully Mhc-Mismatched Limb Allografts after a Short Course of Anti-alpha beta-T Cell Receptor Monoclonal Antibody and FK506

• Kanatani T
• Fujioka H
• Lanzetta M
• Kurosaka M
• Matsumoto
• Bishop GA

Abstract

Whether a seven days course of anti-alpha beta cell receptor-antibody (alpha beta-TCRmAb) combined with FK506 therapy promotes survival of limb allografts in fully MHC-mismatched combination (Brown Norway --> Lewis) was examined. Eight animals received 250 microgram/kg/day of alpha beta-TCRmAb for 7 days and 2 mg/kg/day of FK506 postoperatively (Combination therapy group). Eight animals had FK506 only (Mono-therapy group) and five animals did not have treatment (Control group). Clinical signs of early rejection with edema or erythema in the skin occurred at an average of 8.6+/-1.5 days postoperatively in Control group and 59.0+/-8.3 days in Mono-therapy group, both of which proceeded to irreversible rejection with necrosis of the epidermis and finally mummification. In Combination therapy group, all animals showed evidence of early rejection at an average of 56.8+/-12.6 days postoperatively, however, in 4 of 8 limbs, early rejection resolved without any treatment and limbs survived >1 year. At 9 months postoperatively, donor skin grafts were accepted and third-party skin grafts were rejected by all four survivors, demonstrating donor-specific tolerance. Little or no detectable chimerism was observed in any of the 4 surviving animals at one-year postoperatively. Combination therapy of alphabeta-TCRmAb and FK506 resulted in long-term survival in fully MHC-mismatched limb transplants.

Keyword

Experimental limb transplantation; FK506 and rat

MeSH Terms

Animals
Chimerism
Edema
Epidermis
Erythema
Extremities
Humans
Necrosis
Norway
Rejection (Psychology)
Skin
Survivors
Tacrolimus
Tissue Donors
Transplantation, Homologous
Transplants
Tacrolimus