Systemic overexpression of interleukin-10 fails to protect allogeneic islet transplants in nonobese diabetic mice.
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.
Zhang
Y Clare
YC
Department of Pediatrics, Children's Research Institute, University of South Florida, St. Petersburg, FL, USA.
Pileggi
Antonello
A
Molano
R Damaris
RD
Wasserfall
Clive
C
Campbell-Thompson
Martha
M
Ricordi
Camillo
C
Atkinson
Mark A
MA
Inverardi
Luca
L
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000229:Dependovirus / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013311:Streptozocin / Q000633:toxicity; D014184:Transplantation, Homologous
D000903:Antibiotics, Antineoplastic; D016753:Interleukin-10; D013311:Streptozocin