LIFE AND DEATH OF ANTIGEN ACTIVATED T CELLS IN VIVO

T细胞对入侵生物作出反应的能力， 攻击自己的宿主对宿主的健康至关重要。 众所周知，许多潜在的自身反应性T细胞在淋巴细胞中死亡。 胸腺，在它们成为成熟的功能细胞之前。 一些 然而，自身反应性T细胞逃脱胸腺。 这些细胞必须 被摧毁或失去活性 以前已经表明，许多成熟的T细胞在它们被激活时死亡。 遇到抗原 尽管有人提出了一些假设， 为了解释为什么抗原会导致动物T细胞死亡， 实验尚未完全解释这一现象。 在 在本项目中，要比较的各种机制包括Fas和 RNF受体驱动的死亡，细胞毒性T细胞引起的死亡，死亡 由于遇到抗原不适当的抗原呈递而引起 细胞如B细胞和由于生长因子的撤回而死亡。 接触抗原并不总是杀死抗原特异性T细胞 细胞 有时抗原特异性细胞存活下来， 生产性免疫反应 已经表明，共同暴露于 炎性刺激物如细菌脂多糖和抗原 促进抗原特异性T细胞的分裂和存活。 这 该项目将研究炎症诱导的细胞因子是什么 对拯救抗原刺激的T细胞至关重要。 研究还将 试图找出哪些细胞因子必须直接作用于 拯救T细胞

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.