T-cell-specific immunosuppression results in more than 53 days survival of porcine islets of langerhans in the monkey.
BACKGROUND
Transplantation of islets of Langerhans can restore insulin production in diabetic patients. Because of the shortage of human donor organs, transplantation of porcine islets may be an alternative solution. The present study was aimed at the characterization of rejection mechanisms of porcine islets transplanted into eight nondiabetic monkeys under the kidney capsule.


METHODS
Cultured adult pig islets were used, which showed no expression of the galactose(alpha1,3)galactose epitope, major histocompatibility complex class II, or CD45, and no binding of antibodies or complement after exposure to monkey serum. Immunosuppression consisted of cyclophosphamide, cyclosporine A (CsA), and steroids (group 1); or antithymocyte globulin, anti-interleukin-2 receptor antibody, CsA, and steroids (group 2). In three animals of group 2, islets were also transplanted in the portal vein.


RESULTS
Although all monkeys had preformed anti-pig antibodies, no correlation was found between antibody titers and rejection and no deposition of antibodies or complement was observed in the grafts. Group 1 showed islets up to day 11, followed by T-cell infiltration and rejection at approximately day 14. In group 2, two monkeys showed infiltrates consisting predominantly of T cells starting at approximately day 29, whereas two monkeys showed well-preserved islets without infiltration up to day 53. In the livers of the three monkeys that also received islets intraportally and were resectioned on days 21, 33, and 49, no islets could be detected.


CONCLUSIONS
This study demonstrates that cultured adult pig islets can survive in the monkey for more than 53 days without signs of rejection under standard immunosuppression.
Rijkelijkhuizen
Josephine K R A
JK
Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
Haanstra
Krista G
KG
Wubben
Jacqueline
J
Töns
Annemiek
A
Roos
Anja
A
van Gijlswijk-Janssen
Daniëlle J
DJ
Ringers
Jan
J
Bouwman
Eelco
E
Jonker
Margreet
M
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007273:Injections, Intramuscular; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone