Attenuation of transplant arteriosclerosis by oral feeding of MHC encoding chitosan-DNA nanoparticles is mediated by humoral immunity

C Heim; K Goldmann; S Eckl; M Weyand; BM Spriewald; S Ensminger

doi:10.1055/s-0032-1332450

The Thoracic and Cardiovascular Surgeon, Table of Contents

Attenuation of transplant arteriosclerosis by oral feeding of MHC encoding chitosan-DNA nanoparticles is mediated by humoral immunity

C Heim ¹, K Goldmann ², S Eckl ¹, M Weyand ¹, BM Spriewald ², S Ensminger ¹

¹Department of Cardiac Surgery, Erlangen, Germany
²Department of Medicine 5, Erlangen, Germany

Abstract

Introduction: One promising approach for the induction of transplant tolerance is the pre-treatment of transplant recipients with donor MHC-alloantigen. Our study focuses on the oral delivery of MHC-antigen encoding genes via chitosan-DNA nanoparticles to modulate the allo-immune response in order to reduce the development of transplant arteriosclerosis, the hallmark feature of chronic rejection after heart transplantation.

Methods: We performed fully allogeneic mouse abdominal aortic transplantats using C57BL/6 (H2^b) mice as donors and CBA.J (H2^k) mice as recipients Aortic grafts were analyzed by histology and morphometry on day 30 after transplantation, levels of circulating alloantibodies were detected by FACS analysis.

Results: Pre-treatment of recipient mice with chitosan-DNA nanoparticles encoding for K^b, one of the MHC-I molecules of the donor, resulted in a significant reduction of intimal proliferation compared to untreated controls. When Ovalbumin was fed instead of K^b encoding nanoparticles (K^b-NP) or Balb/c (H2^d) grafts were used instead of C57BL/6 (H2^b) grafts as antigen controls, both groups showed no reduction of intimal thickness indicating an antigen-specific mechanism. In addition, analysis of peripheral blood of the transplanted mice showed significant suppression of alloantibody formation in the K^b-NP fed group compared to all other allogeneic transplanted groups suggesting modulation of the humoral immune response.

Conclusion: These results demonstrate the potential of chitosan-DNA nanoparticles to induce K^b-specific tolerance and to reduce the development of transplant arteriosclerosis.