Systemic overexpression of interleukin-10 fails to protect allogeneic islet transplants in nonobese diabetic mice.

Abstract

Interleukin (IL)-10 has proven effective in various allogeneic transplantation models and for preventing recurrent autoimmune rejection of syngeneic islets in NOD mice. Therefore, we evaluated systemic IL-10 overexpression on allogeneic islet graft survival. Diabetic NOD mice received a single injection of recombinant adeno-associated virus (rAAV) serotype 2 encoding murine IL-10 (rAAV-IL-10) four weeks prior to renal subcasular islet transplantation. In a model having both autoimmune and allogeneic responses, IL-10 failed to protect C57BL/6 islets in spontaneously diabetic NOD mice. In an allograft model (C57BL/6 islets into young male streptozotocin-induced diabetic NOD mice), long-term (i.e., >169 days) islet survival was only seen in 2 of 14 rAAV-IL-10 treated mice. These failures occurred despite in vivo IL-10 production at transplant previously associated with protection of syngeneic islet grafts in NOD mice. Thus, IL-10 appears insufficient in protecting transplanted islet cells from allogeneic rejection and suggests important mechanistic variances between alloreactivity and autoimmunity in terms islet graft loss.