The long term objective of this proposal is to identify and characterize the T cells responsible for causing autoimmune type I diabetes. By identifying the specific populations involved, more precise intervention approaches can be employed to prevent the development of the disease. As has been determined to be a central theme of all projects in this proposal, we have identified a link between apoptosis and autoimmune disease. Specifically, we conclude from our studies of diabetes prone BB- DP rats that the autoreactive T cells are resistant to apoptosis and anergy induction and they are best characterized as medullary thymocytes rather than mature peripheral T cells. Our working hypothesis is that the resistant phenotype is associated with the way in which these thymocytes escape the normal selection process that deletes self reactive T cells in the thymus. This resistance to anergy and apoptosis is a critical characteristic of an autoreactive """"""""medullary thymocyte"""""""" subset involved in the development of autoimmune diabetes.
The specific aims of this proposal will focus on the genetic contribution of diabetes susceptibility genes to the characteristics ascribed to the autoreactive T cells and determining if the autoreactive T cells can be isolated from the thymus of diabetes prone and non diabetic animals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK048805-03
Application #
2016869
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Akolkar, Beena
Project Start
1994-12-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Moore, J K; Bellgrau, D (1999) Promiscuous activation and cell cycle entry in T cells from autoimmune animals. Transplant Proc 31:1606-10
Moore, J K; Gold, D P; Dreskin, S C et al. (1999) A diabetogenic gene prevents T cells from receiving costimulatory signals. Cell Immunol 194:90-7