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Split tolerance to a composite tissue allograft in a swine model
David W Mathes1, Mark A Randolph, Mario G Solari
1Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Transplantation
|January 25, 2003
Summary
Composite tissue transplantation faces skin antigenicity challenges. This study found that while 12-day cyclosporine treatment induced tolerance to vascularized musculoskeletal allografts in swine, skin graft survival was prolonged but not indefinite, suggesting isolated immune reactions to the epidermis.
Area of Science:
- Transplantation immunology
- Composite tissue allografts
- Immunosuppression strategies
Background:
- Skin antigenicity is a significant barrier in composite tissue transplantation, leading to rejection episodes.
- Previous studies showed tolerance to vascularized musculoskeletal allografts with cyclosporine but not to non-vascularized skin grafts.
- The study aimed to assess tolerance to limb allografts including a vascularized skin component.
Purpose of the Study:
- To evaluate the efficacy of a 12-day cyclosporine regimen combined with MHC matching in achieving tolerance to vascularized limb allografts.
- To determine if this immunosuppression protocol could induce tolerance to the skin component of the allograft.
- To investigate the immune response to the skin versus the musculoskeletal portion of the allograft.
Main Methods:
- Heterotopic hind limb transplantation in MHC-matched miniature swine (n=6) with a cutaneous paddle.
- All animals received a 12-day course of cyclosporine; one control received no immunosuppression.
- Graft evaluation via biweekly biopsies and histological analysis; testing for sensitization with secondary frozen donor skin grafts.
Main Results:
- All immunosuppressed animals achieved indefinite survival of the musculoskeletal allograft component (>100 days).
- Epidermal survival was prolonged in five animals, with one showing tolerance for over 180 days.
- Control animal rejected the epidermis at 10 days; secondary skin grafts showed accelerated rejection, indicating an isolated immune response to the skin.
Conclusions:
- A short-term cyclosporine course with MHC matching induces lasting tolerance to the musculoskeletal component of vascularized allografts.
- The skin component, particularly the epidermis, elicits an isolated immune response, leading to prolonged but not indefinite survival.
- These findings highlight the distinct immunogenicity of skin within composite tissue allografts and suggest targeted strategies may be needed.