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

免疫系统通过称为淋巴细胞的循环白色血细胞群体来保护身体免受感染。每个淋巴细胞表面都有自己的受体，它只能识别可能存在的物质中的一种。受体以半随机的方式产生，使用基因编码的元件组合，并且有可能产生与身体本身反应的受体，而不是与入侵的生物体反应。如果携带这些自身反应受体的细胞被激活，就会引发自身免疫性疾病。淋巴细胞如何区分机体本身和外来生物体的问题是免疫学家最感兴趣的。最初的想法之一是，自我反应淋巴细胞在生命早期的反应中被灭活。尽管这一观点简单明了，在智力上也很有吸引力，但它与大量的实验证据并不一致。在大量新实验的基础上，我提出了一个淋巴细胞亚群自身耐受的替代模型。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外来物质的特性，并将这些信息传递下去。本项目的目的是为支持这个模型提供直接的实验证据。我们许多试图解决与免疫系统相关的医学问题的努力都受到了阻碍，因为我们对免疫耐受是如何控制的缺乏了解。如果我的模型被证明是正确的，就有可能以更大的效率操纵免疫反应，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。

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.