The investigators have developed a large animal model of cardiac allograft vasculopathy using partially inbred miniature swine, which differ from rodents in their immune responses, cardiovascular physiology and susceptibility to atherosclerosis. Preliminary data demonstrate that coronary lesions develop in hearts transplanted across a class I or full MHC barrier, but not in hearts transplanted across a class II MHC barrier or in hearts matched at the entire MHC. Furthermore, vasculopathy is prevented when recipients are rendered tolerant to the donor class I alloantigens. Based on these findings, the investigator proposes five specific aims: 1) Determine the immunogenetic requirements for the development of cardiac allograft vasculopathy in miniature swine; 2) Determine the pathways of cellular immunity which induce coronary lesions in MHC class I disparate but not class I disparate hearts by extracting and analyzing graft infiltrating cells; 3) Determine whether humoral antibodies contribute to vasculopathy in class I mismatched cardiac grafts using flow cytometry, cytotoxicity assays, and antibody transfer techniques; 4) Assess the role of selected cytokines and adhesion molecules in the induction of cardiac allograft vasculopathy using Northern blot analysis; 5) Evaluate the efficacy of anti CD8 monoclonal antibody in preventing or reversing vasculopathy in transplanted hearts using the pig monoclonal antibody 76 2 11.
| Meltzer, A J; Veillette, G R; Aoyama, A et al. (2012) Donor brain death inhibits tolerance induction in miniature swine recipients of fully MHC-disparate pulmonary allografts. Am J Transplant 12:1290-5 |
| Veillette, Gregory R; Sahara, Hisashi; Meltzer, Andrew J et al. (2011) Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine. Transplantation 91:1187-91 |
| Hirohashi, T; Uehara, S; Chase, C M et al. (2010) Complement independent antibody-mediated endarteritis and transplant arteriopathy in mice. Am J Transplant 10:510-7 |
| Weiss, M J; Guenther, D A; Mezrich, J D et al. (2009) The indirect alloresponse impairs the induction but not maintenance of tolerance to MHC class I-disparate allografts. Am J Transplant 9:105-13 |
| Ng, Choo Y; Madsen, Joren C; Rosengard, Bruce R et al. (2009) Immunosuppression for lung transplantation. Front Biosci (Landmark Ed) 14:1627-41 |
| Weiss, Matthew J; Madsen, Joren C; Rosengard, Bruce R et al. (2008) Mechanisms of chronic rejection in cardiothoracic transplantation. Front Biosci 13:2980-8 |
| Hoerbelt, Ruediger; Benjamin, Christopher L; Shoji, Tsuyoshi et al. (2008) The effects of tolerance on allograft damage caused by the innate immune system. Transplantation 85:314-22 |
| Houser, Stuart; Muniappan, Ashok; Allan, James et al. (2007) Cardiac allograft vasculopathy: real or a normal morphologic variant? J Heart Lung Transplant 26:167-73 |
| Hoerbelt, R; Benjamin, L C; Shoji, T et al. (2006) Effects of tolerance induction on the actions of interferon-gamma on porcine cardiac allografts. Transplant Proc 38:3196-8 |
| Weiss, Matthew J; Ng, Choo Y; Madsen, Joren C (2006) Tolerance, xenotransplantation: future therapies. Surg Clin North Am 86:1277-96, viii |
Showing the most recent 10 out of 38 publications
