Population dynamics of tissue-specific effector and regulatory CD4+ T cells

白细胞在体内的存活是一个活跃的过程，对维持能够识别各种外来抗原的T细胞群很重要。目前，识别自身抗原的T淋巴细胞的命运尚不清楚。了解自身反应性T淋巴细胞的生存动力学及其在正常人体内的调控机制，对于控制包括自身免疫性疾病在内的各种疾病的发展至关重要。从我们之前对自身免疫性胃炎的研究中，我们已经产生了识别胃特异性抗原的淋巴细胞细胞系，并将利用这些独特的试剂进行实验，以确定这些自我反应性T细胞在正常个体中的命运。此外，我们还将确定不同数量的组织抗原对自身反应性T细胞存活和激活的影响，最后确定一类特殊的淋巴细胞，即调节性淋巴细胞，如何在体内发挥作用来控制自身反应性T细胞的活动。我们将不仅使用经典的免疫学方法来解决这些问题，而且还将使用最先进的成像技术，以可视化活组织中细胞相互作用的性质。这项工作产生的信息将支持选择性关闭导致疾病的自我反应性淋巴细胞的策略，将形成基于细胞的治疗自身免疫性疾病的临床开发的基础，并且在这项赠款中开发的成像技术将广泛适用于一系列免疫反应的研究。

Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. From our previous studies of autoimmune gastritis we have generated cell lines of lymphocytes that recognise stomach-specific antigens and with these unique reagents we will perform experiments to determine the fate of these self-reactive T cells in a normal individual. Also we will determine the impact of different amounts of the tissue antigens on the survival and activation of self-reactive T cells, and finally how a special class of lymphocytes, know as regulatory lymphocytes, act in vivo to control the activity of self-reactive T cells. We will use not only classical immunological approaches to address these issues but also state of the art imaging, to visualise the nature of the cell interactions in living tissues. The information arising from this work will underpin strategies to selectively turn off self-reactive lymphocytes that cause disease, will form the basis of clinical development of cell based therapies to treat autoimmune diseases, and the imaging technologies developed in this grant will have wide applicability to the study of a range of immune responses.