The ability of T cells to respond to invading organisms but not to attack their own host is crucially important to the health of the host. It is known that many potentially autoreactive T cells die in the thymus, before they become mature functional cells. Some autoreactive T cells escape the thymus however. These cells must be destroyed or inactivated. It has previously been shown that many mature T cells die when they encounter antigen. Although some hypotheses have been put forward to explain why antigen causes T cell death in animals, no experiments have yet accounted for the phenomenon completely. In this project the various mechanisms to be compared include Fas and RNF receptor-driven death, death caused by cytotoxic T cells, death caused by encounter with antigen on inappropriate antigen presenting cells such as B cells and death due to withdrawal of growth factors. Encounter with antigen does not always kill the antigen specific T cells. Sometimes antigen specific cells survive to give rise to productive immune responses. It has been shown that co-exposure to inflammatory stimuli such as bacterial lipopolysaccharide and antigen promotes the division and survival of antigen specific T cells. This project will investigate what cytokines induced by inflammation are critical to the rescue of antigen stimulated T cells. Studies will also be done to try to find out what cytokines must act directly on the rescued T cells themselves.
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