Vascularized thymic lobe transplantation in miniature swine: I. Vascularized thymic lobe allografts support thymopoiesis.
BACKGROUND
Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine.


METHODS
Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naïve minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74-12-4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells.


RESULTS
Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60.


CONCLUSIONS
Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts.
LaMattina
John C
JC
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Kumagai
Naoki
N
Barth
Rolf N
RN
Yamamoto
Shin
S
Kitamura
Hiroshi
H
Moran
Shannon G
SG
Mezrich
Joshua D
JD
Sachs
David H
DH
Yamada
Kazuhiko
K
D000818:Animals; D006410:Hematopoiesis; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000098:blood supply* / Q000637:transplantation*; D014184:Transplantation, Homologous