Donor-specific tolerance induced by simultaneous allogeneic islet transplantation with CD4+CD25+T-cells into hepatic parenchyma in mice

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Abstract
Background. The allogeneic islets transplantation is an ideal therapeutic strategy for patients with diabetes mellitus. However, it has been difficult to induce immunological tolerance against islets grafts. The CD4+CD25+ regulatory T-cells (Treg) play a role in suppressing T-cell activation. Thus, we evaluated whether Treg can regulate donor-specific T-cell tolerance that received allogeneic islets into the hepatic parenchyma (ITxHP) along with Treg. Methods. C3 H/He mice were used as donors ; and streptozotocin-induced diabetic BALB/c mice were recipients. The protocol included three groups : Group A recipients received only 300 IE islets ; Group B was given 300 IE islets and whole splenocytes ; Group C was given 300 IE islets and Treg purified from peripheral lymph nodes. Results. For all mice in Groups A and B, the fasting blood sugar exceeded 250mg/dl and graft rejection was observed. GVHD was observed earlier in Group B than in Group A. In contrast graft survival exceeded 30 days for two mice in Group C (50%, mean POD 28.5±24.0, PConclusions. The simultaneous ITxHP with CD4+CD25+ T-cells administration prolonged islet graft survivals and induced donor-specific hyporesposiveness.