Abstract

The objective of the project is to study a syndrome of spontaneous onset diabetes in rats, which appears to be the animal model most closely resembling human insulin dependent diabetes. Preliminary studies indicate autoimmunity is very likely to play a role in pathogenesis and appears to cause destruction of transplanted pancreatic islets even if rejection is prevented.
Specific aims of the grant include study and manipulation of the genetic setting of the disease and attempts to confirm the autoimmune nature by transferring the condition to non diabetic rats by means of """"""""immune"""""""" lymphocytes. Diabetic and prediabetic rats hve been found to have some characteristics of immune deficiency. We will attempt to define the responsible factors (e.g. abnormal T cell function) in the immunodeficiency and to determine whether it is causally related to the diabetes. We will also investigate possible reasons for our observation that transplantation of bone marrow from normal donors to members of the diabetes prone stock decreases the incidence of diabetes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK026007-08
Application #
3227692
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1979-06-01
Project End
1987-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
8
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

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
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
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
Markmann, J F; Bassiri, H; Desai, N M et al. (1993) Donor antigen-specific T-lymphocyte deletion after intrathymic inoculation. Transplant Proc 25:305-6
Barker, C F; Posselt, A M; Odorico, J S et al. (1993) Intrathymic transplantation as a model for tolerance. Adv Nephrol Necker Hosp 22:387-400
Markmann, J F; Bassiri, H; Desai, N M et al. (1992) Indefinite survival of MHC class I-deficient murine pancreatic islet allografts. Transplantation 54:1085-9

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