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.