The role of dendritic cell subsets in the decision between T cell tolerance and immunity

树突状细胞亚群在 T 细胞耐受和免疫决策中的作用

• 批准号: nhmrc : 115050
• 负责人: Prof Barbara Fazekas De St Groth
• 金额: $ 29.67万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-dendritic-cell-tolerance-immunity/81297
• 关键词: role; dendritic; cell; subsets; decision

The immune system protects the body against infection by means of a population of circulating white blood cells called lymphocytes. Each lymphocyte has on its surface its own particular receptor which recognises only one out of the universe of possible substances. Receptors are generated in a semi-random way, using a combination of elements encoded by the genes, and it is possible to generate receptors that react with the body itself, rather than with invading organisms. If the cells bearing these self-reactive receptors become activated, an autoimmune disease ensues. The question of how lymphocytes can tell the difference between the body itself and foreign organisms is of major interest to immunologists. One of the first ideas was that self-reactive lymphocytes are inactivated by making reactions early in life. Despite the simplicity and intellectual appeal of this idea, it is inconsistent with a large body of experimental evidence. On the basis of number of new experiments, I have proposed an alternative model of self tolerance for one of the subsets of lymphocytes. In this model, the cells that help lymphocytes to recognise particular substances possess the property of distinguishing self from foreign, and pass that information on. The aim of this project is to provide direct experimental evidence in support of the model. Many of our attempts to deal with medical problems related to the immune system have been hampered by our lack of understanding of exactly how immune tolerance is controlled. If my model proves to be correct, it will be possible to manipulate immune responses with far greater effectiveness, providing new treatments for autoimmune disease, allergy, graft rejection and vaccination.

免疫系统通过称为淋巴细胞的循环白细胞群来保护身体免受感染。每个淋巴细胞的表面都有自己特定的受体，该受体只能识别所有可能物质中的一种。受体是使用基因编码的元素组合以半随机方式生成的，并且可以生成与身体本身而不是入侵生物体发生反应的受体。如果携带这些自身反应受体的细胞被激活，就会发生自身免疫性疾病。淋巴细胞如何区分身体本身和外来生物体的问题是免疫学家最感兴趣的问题。第一个想法是，自反应淋巴细胞通过在生命早期做出反应而失活。尽管这个想法简单且具有智力吸引力，但它与大量实验证据不一致。在大量新实验的基础上，我提出了一种针对淋巴细胞亚群之一的自我耐受的替代模型。在这个模型中，帮助淋巴细胞识别特定物质的细胞具有区分自身和异物的特性，并传递该信息。该项目的目的是提供直接的实验证据来支持该模型。由于我们对免疫耐受的确切控制方式缺乏了解，我们处理与免疫系统相关的医学问题的许多尝试都受到了阻碍。如果我的模型被证明是正确的，就有可能以更有效的方式操纵免疫反应，为自身免疫性疾病、过敏、移植排斥和疫苗接种提供新的治疗方法。