Vascularized composite allograft transplant survival in miniature swine: is MHC tolerance sufficient for acceptance of epidermis?

Journal Article

Background

We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC-matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs).

Methods

Group 1 animals (n=3) received donor MHC-matched VCAs less than 70 days after primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched kidney transplant followed by a donor-matched VCA more than 200 days after primary KTx.

Results

Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of three recipients of VCAs in Group 2, accepted all components of the VCA, including epidermis (>200 days). The other two recipients lost only the epidermis on days 45 and 85, with survival of the remainder of the VCA long-term.

Conclusions

All tissues of a VCA are accepted long-term on animals tolerant of class I-mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared with split-thickness skin grafts but not indefinite. Exposure of tolerant animals to second donor-matched kidneys before VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney.

Full Text

Duke Authors

Cited Authors

  • Cetrulo, CL; Torabi, R; Scalea, JR; Shimizu, A; Leto Barone, AA; Gillon, BC; Tasaki, M; Leonard, DA; Cormack, TA; Villani, V; Randolph, MA; Sachs, DH; Yamada, K

Published Date

  • December 2013

Published In

Volume / Issue

  • 96 / 11

Start / End Page

  • 966 - 974

PubMed ID

  • 24056624

Pubmed Central ID

  • 24056624

Electronic International Standard Serial Number (EISSN)

  • 1534-6080

International Standard Serial Number (ISSN)

  • 0041-1337

Digital Object Identifier (DOI)

  • 10.1097/tp.0b013e3182a579d0

Language

  • eng