| Ligation of the T cell receptor (TCR) by self-antigen/MHC complexes results in T cell activation or tolerance, leading to autoimmunity or protection, respectively. The factors however, that contribute to either outcome are not well defined. We hypothesize that the balance between the induction of autoimmunity and tolerance may be a function of the lifespan of the antigen presenting cell (APC) presenting self-antigen, where prolonged survival promotes the induction of autoimmunity and shortened survival promotes the induction of tolerance. To assess the affect of APC lifespan on T cell activation, dendritic cells (DC) of increased lifespan and shortened lifespan, relative to normal DC, were generated and assessed for their ability to activate antigen-specific T cells. DC generated from bone marrow (BM) of normal mice and treated with ceramide (C2) as well as BM-DC generated from CD40-deficient mice (CD40-/-) were utilized as DC with shortened lifespans. BM-DCs of normal mice were treated with a general caspase inhibitor (APO-Block) to generate DC with prolonged life spans. (Abstract shortened by UMI.)... |
