A peptide-major histocompatibility complex ii chimera favors survival of pancreatic β-?slets grafted in type 1 diabetic mice

Sofia Casares, Marvin Lin, Nan Zhang, John R. Teijaro, Cristina Stoica, Robert McEvoy, Donna L. Farber, Constantin Bona, Teodor D. Brumeanu

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5 Scopus citations


BACKGROUND.: Transplantation of pancreatic islets showed a tremendous progress over the years as a promising, new therapeutic strategy in patients with type 1 diabetes. However, additional immunosuppressive drug therapy is required to prevent rejection of engrafted islets. The current immunosuppressive therapies showed limited success in maintaining long-term islet survival as required to achieve insulin independence in type 1 diabetes, and they induce severe adverse effects. Herein, we analyzed the effects of a soluble peptide-major histocompatibility complex (MHC) class II chimera aimed at devising an antigen-specific therapy for suppression of anti-islet T cell responses and to improve the survival of pancreatic islets transplants. METHODS.: Pancreatic islets from transgenic mice expressing the hemagglutinin antigen in the beta islets under the rat insulin promoter (RIP-HA) were grafted under the kidney capsule of diabetic, double transgenic mice expressing hemagglutinin in the pancreas and T cells specific for hemagglutinin (RIP-HA, TCR-HA). The recipient double transgenic mice were treated or not with the soluble peptide-MHC II chimera, and the progression of diabetes, graft survival, and T cell responses to the grafted islets were analyzed. RESULTS.: The peptide-MHC II chimera protected syngeneic pancreatic islet transplants against the islet-reactive CD4 T cells, and prolonged the survival of transplanted islets. Protection of transplanted islets occurred by polarization of antigen-specific memory CD4 T cells toward a Th2 anti-inflammatory response. CONCLUSIONS.: The peptide-MHC II chimera approach is an efficient and specific therapeutic approach to suppress anti-islet T cell responses and provides a long survival of pancreatic grafted islets.

Original languageEnglish
Pages (from-to)1717-1725
Number of pages9
Issue number12
StatePublished - 27 Jun 2008
Externally publishedYes


  • Islets
  • Islets protection
  • Pancreas
  • Peptide-MHC II chimera
  • Transplantation


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