Primary attention is focused on experiments to define the immune pathogenesis of spontaneous diabetes in the BB rat, an animal model with many features in common with the human disease. Since we have found that transplanted islets succumb to the same autoimmune damage which destroys the native islets, islet grafts will be employed as a probe to investigate the phenomenon of MHC restriction in autoimmune islet damage. Employing inbred and congenic strains of rats attempts will be made to locate the region of MHC responsible for restriction phenomena. The fate of antigen presenting cell depleted islet grafts will be studied in immunologically tolerant hosts to identify and characterize the activity of effector cells involved in islet damage. Investigations are also planned to determine whether the islet damage seen in these tolerant hosts is caused by an aberrant differentiation of normal stem cells in an autoimmune milieu which results in autoreactive cells in these hosts. Examination of the role of thymic education of T cells and MHC restriction patterns of diabetogenic effector cells is a major goal of the grant. Aspects of the proposed studies which are of possible immediate practical importance are: 1) perfection of islet transplant techniques; 2) markers for prediabetic states; 3) development of safe and effective immunosuppression as treatment or prophylaxis of diabetes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
DeMatteo, R P; Yeh, H; Friscia, M et al. (1999) Cellular immunity delimits adenoviral gene therapy strategies for the treatment of neoplastic diseases. Ann Surg Oncol 6:88-94
DeMatteo, R P; Chu, G; Ahn, M et al. (1997) Long-lasting adenovirus transgene expression in mice through neonatal intrathymic tolerance induction without the use of immunosuppression. J Virol 71:5330-5
Chu, G; Markmann, J F; Ahn, M et al. (1997) Xenogeneic but not allogeneic pancreatic islet graft survival in recipients lacking humoral immunity and major histocompatibility complex class II antigens. Transplant Proc 29:901-2
Ahn, M; Sohn, C; Chang, E et al. (1996) Role of humoral immunity in pancreatic islet allo- and xenograft rejection. Transplant Proc 28:840-1
DeMatteo, R P; Raper, S E; Ahn, M et al. (1995) Gene transfer to the thymus. A means of abrogating the immune response to recombinant adenovirus. Ann Surg 222:229-39;discussion 239-42
Ahn, M; Chang, E; Chu, G et al. (1995) Cellular requirements for pancreatic islet xenograft rejection. Transplant Proc 27:3302-3
Markmann, J F; Desai, N M; Bassiri, H et al. (1994) Prolonged survival of class I deficient mouse islet allografts but not xenografts. Transplant Proc 26:748
Campos, L; Alfrey, E J; Posselt, A M et al. (1993) Intrathymic inoculation of donor cells promotes survival of rat orthotopic liver allografts. Transplant Proc 25:488-9
Markmann, J F; Odorico, J S; Bassiri, H et al. (1993) Deletion of donor-reactive T lymphocytes in adult mice after intrathymic inoculation with lymphoid cells. Transplantation 55:871-6;discussion 876-7
Posselt, A M; Barker, C F; Friedman, A L et al. (1993) Intrathymic inoculation of islets at birth prevents autoimmune diabetes and pancreatic insulitis in the BB rat. Transplant Proc 25:301-2

Showing the most recent 10 out of 24 publications