IMMUNE PRIVILEGE OF THE TESTIS FOR ISLET XENOTRANSPLANTATION (RAT TO MOUSE)

The testis has been suggested as an immune privileged site for islet t ransplantation. The present study evaluated this hypothesis by transpl anting islets from Wistar Furth rats into (a) the testes; (b) the subc apsular space of the kidneys; or (c) the cryptorchid abdominal testes of streptozotocin-induced diabetic Swiss ND4 mice. Transplantation of 800 rat islets into the cryptorchid testes normalized blood glucose fo r 9.3 +/- 1.4 (Mean +/- SD) days, not significantly different from tha t of the scrotal testis site (12.4 +/- 1.3), or when the subcapsular s pace of the kidneys was used (11.5 +/- 1.2). When mouse islets were is otransplanted into the cryptorchid testes of diabetic mice, normoglyce mia was maintained for the entire 3 month study period. Histologic exa mination of the islet xenograft-bearing cryptorchid testes at day 7 po st transplantation and 2 days after returning to hyperglycemia reveale d lymphocyte infiltration surrounding and inside the graft. No lymphoc yte infiltration was seen in the isograft bearing-testes at 3 mo after transplantation. Cyclosporine A (CsA, 15 mg/kg/day) administration to the islet xenograft recipient slightly prolonged the normoglycemic pe riod to 13.7 +/- 1.8 days (p < 0.01). Increasing CsA dose to 25 mg/kg induced a 66% (4/6) mortality, and did not further prolong the normogl ycemic period. Using a lower number of rat islets (200 or 400 islets), prolonged graft survival was achieved in some (4 out of 20) animals w hen the cryptorchid testis was used. In contrast, transplantation of 4 00 Fat islets into the subcapsular space of the kidneys was not associ ated with prolonged graft survival. When a second Fat islet xenograft was transplanted into the subcapsular space of the kidneys of diabetic mice, subsequent to a rejected first intratesticular xenograft, the n ormoglycemic period was markedly shortened to 3.2 +/- 0.5 days (p < 0. 01). It is concluded that the testis mag act as an immune privileged s ite for islet xenotransplantation, however, only when a small number o f islets is transplanted. A large number of islets will override the i mmune privilege status of the testis. CsA slightly but significantly d elays islet xenograft rejection. Finally, islets transplanted in the t estes do sensitize the host against a second islet graft..