Abdominal Intratesticular Islet-Xenograft Survival in Rats

Abstract

We investigated the survival of islet xenografts in the abdominal testes of normal, diabetes-resistant ACl and Wistar-Lewis (W-L) and in diabetes-prone BB/Wor rats. Islets were isolated from hamster donors, and after a period in tissue culture, they were injected into the abdominal testes of diabetic rats. Postoperatively, the rats were divided into two treatment groups. Four ACl rats received antilymphocyte serum (ALS) injections over a period of 30 days, and 13 ACl, 15 W-L, and 13 BB/Wor rats were given cyclosporin (CsA) according to the following regimen: 25 mg/kg i.p. for 7 days, then 7 mg/kg i.p. for 23 days. On day 30, immunosuppression was stopped. The results showed that none of the ALS-treated ACl rats remained normoglycemic for greater than 9 days. However, CsA therapy resulted in an extended mean duration of normoglycemia in the ACl and W-L rats of 160.0 +/- 36.0 and 131.0 +/- 31 days, respectively. By contrast, the mean duration of normoglycemia in the BB/Wor rats was 33.0 +/- 4.0 days. Furthermore, all of the BB/Wor rats reverted to diabetes after CsA was stopped. Therefore, the concomitant administration of an antigenic islet xenograft with CsA led to a state of unresponsiveness only in diabetes-resistant but not in diabetes-prone rats. Because the BB/Wor rats have demonstrable T-lymphocyte dysfunction, they may be unable to generate the CsA-induced suppressor T-lymphocytes required for the long-term acceptance of the graft by the host.