My research proposal will investigate the role of costimulatory molecules, in particular CTLA-4, in tolerance induction and autoimmunity. Costimulatory molecules have a pivotal role in T cell activation and induction of tolerance. The striking phenotype of the CTLA-4-deficient strain demonstrates a key role for CTLA-4 in down-regulating T cell activation and suggests that CTLA-4 is involved in regulating autoimmune responses. In this proposal, I will investigate the in vivo role of CTLA-4 to exogenous and autoantigens using novel transgenic strains as a tool. Our studies will examine whether CTLA-4 regulates T helper cell differentiation in response to exogenous administration of antigen and whether it is possible to tolerize CTLA deficient T cells. Additionally, the role of CTLA-4 in the development of autoimmune responses will be examined using altered peptide ligands and TCR transgenic mice. These studies should provide insights into the regulatory role of CTLA-4 in tolerance and autoimmunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI010415-02
Application #
6422173
Study Section
Special Emphasis Panel (ZRG1-IMB (01))
Program Officer
Prograis, Lawrence J
Project Start
2001-03-01
Project End
Budget Start
2001-03-01
Budget End
2001-06-30
Support Year
2
Fiscal Year
2001
Total Cost
$14,232
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Greenwald, Rebecca J; Oosterwegel, Mariette A; van der Woude, Diane et al. (2002) CTLA-4 regulates cell cycle progression during a primary immune response. Eur J Immunol 32:366-73
Greenwald, R J; Boussiotis, V A; Lorsbach, R B et al. (2001) CTLA-4 regulates induction of anergy in vivo. Immunity 14:145-55