Figure 4

Islet allograft survival after CsA and TMC injection as an immunosuppressant. (A) The duration of graft survival following transplantation of allogeneic islets was defined until the last day of normoglycemia (<200 mg/kg). Group 1 (control, ◯, n = 9) received islets without immunosuppressant. Group 2 (△, n = 6) and group 3(▲, n = 10) rats were treated with CsA only (5 mg/kg) or high-dose TMC only (0.1 mg/kg), respectively. Group 4 (♦, n = 4) and group 5 (■, n = 5) rats were cotreated with CsA and TMC; group 4 received low-dose TMC (0.03 mg/kg). Group 5 received high-dose TMC (0.1 mg/kg), and both groups received the same subtherapeutic dose of CsA (5 mg/kg). All the recipients in each group were injected with relevant immunosuppressant intraperitoneally for 2 wks (*P < 0.05 versus others). (B) On d 70 after islet transplantation, rats were subjected to intravenous glucose tolerance tests to determine the function of transplanted islets. Rats fasted for 4 h and were injected with 2 mg/kg glucose via a tail vein. Blood glucose was measured immediately prior to and 5, 10, 15, 20, 30, 45, 60, 90 and 120 min after intravenous administration of glucose (2 g/kg). (C) On d 107 after islet transplantation, pancreas and liver sections were examined by light microscopy. Upper panel, hematoxylin and eosin staining. Lower panel, immunohistochemical staining for insulin (original magnification 200×). (D) The recipient liver biopsy samples obtained on d 5 after islet transplantation in control and CsA and TMC cotreated group. CD4⁺ (arrowhead) and CD8⁺ (arrow) T-lymphocyte infiltration were determined by immnunohistochemical staining using anti-CD4 and anti-CD8 monoclonal antibodies.