CD4+CD25+ regulatory T cells play a major role in the control of immunity, as the lack of this T cell population results in the activation of autoreactive T cells and the development of autoimmune diseases. It has been reported that the level of CD4+CD25+ regulatory T cells is lower in autoimmune-prone mice such as NZBxNZWFI (BWF1) and NOD mice. The central hypothesis of this proposal is that autoimmune-prone mice may have a defect in CD4+CD25+ regulatory T cell function, which may play a role in the pathogenesis of autoimmune diseases. Our preliminary studies suggest that NOD antigen presenting cells (APC) play a crucial role in the defect of CD4+CD25+ regulatory T cell function, but that activation of NOD APC restores normal regulation in vivo. The objective of this proposal is, therefore, to develop novel strategies using TLRs to restore optimal regulation in NOD mice, and to characterize the mechanisms of this regulation. Moreover, we will investigate whether APC from diabetic patients have also a defect in activating regulatory T cells, and whether enhancement of thejr APC function can ameliorate regulation, as well as whether regulatory T cells from diabetic patients can be activated directly via TLRs. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
3F31AI064120-01A1S1
Application #
7176361
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hernandez, Milton J
Project Start
2005-08-01
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$1,944
Indirect Cost
Name
University of Louisville
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292