The role members of the T cell, immunoglobulin domain, mucin domain (Tim) family of proteins play in immunity is quickly unfolding. Tim-4 was recently shown to be expressed by antigen-presenting cells and is a ligand for another member of the protein family, Tim-1, which is expressed on activated T cells. Preliminary in vivo data using both Tim-1Ig and Tim-4lg fusion proteins and in vitro data using Tim-4-transfectant artificial antigen-presenting cells suggests that this interaction is costimulatory. I propose to carry out in vivo and in vitro studies to investigate (i) the temporal and regional expression of Tim-4 in animals undergoing EAE; (ii) a potential role for Tim-4 expression during the induction of or relapse of EAE; (iii) the molecular mechanism behind this phenomenon. These studies will help uncover whether Tim-4 plays a role in inducing autoimmune disease by stimulating pathogenic T cell stimulation. These studies will help determine whether Tim-1 and Tim-4 play a role in the induction of autoimmune disease. Data from this research may lead to the development of novel therapies for the treatment of T cell mediated autoimmune diseases, such as multiple sclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS056503-03
Application #
7473104
Study Section
Special Emphasis Panel (ZRG1-IMM-L (29))
Program Officer
Utz, Ursula
Project Start
2006-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$30,723
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Rodriguez-Manzanet, Roselynn; Sanjuan, Miguel A; Wu, Henry Y et al. (2010) T and B cell hyperactivity and autoimmunity associated with niche-specific defects in apoptotic body clearance in TIM-4-deficient mice. Proc Natl Acad Sci U S A 107:8706-11
Rodriguez-Manzanet, Roselynn; Meyers, Jennifer Hartt; Balasubramanian, Savithri et al. (2008) TIM-4 expressed on APCs induces T cell expansion and survival. J Immunol 180:4706-13