Regulation of T cell homeostasis by antigen receptor signals and interleukin-7

免疫系统在保护个人免受细菌、病毒和其他致病原体的寄生虫感染方面发挥着至关重要的作用。T淋巴细胞是免疫细胞，在调节免疫反应方面发挥关键作用，如果要正常发挥作用，拥有足够数量的T淋巴细胞是至关重要的。在免疫系统中发现的T细胞的数量受到控制T细胞的生产、生存和复制的过程的仔细调节。了解这些过程是如何工作的很重要，因为当它们出错时，产生太多或错误类型的T细胞可能会导致糖尿病等自身免疫性疾病，或者导致白血病或其他癌症的发展。了解我们的身体是如何控制T细胞数量的，对于开发T细胞数量丢失的治疗方法也具有临床意义，例如在艾滋病患者中，对于接受癌症治疗的人来说，这些患者会产生不必要的副作用，杀死T细胞，或者确实有助于骨移植患者的重建。所有的T细胞都表达一种表面蛋白，即T细胞抗原受体(TCR)，使T细胞能够识别和记忆外来病原体。然而，来自同一受体的信号也参与控制T细胞的生存和复制过程，这些过程涉及控制免疫系统的大小。此外，可溶性免疫激素白介素7(IL7)也参与调节这些相同的过程，并与TCR信号一起工作。我们工作的目的是更深入地了解这两个因素是如何控制T细胞的存活和复制的。为了做到这一点，我们开发了小鼠模型，在这种模型中，我们可以专门控制T细胞是从TCR还是从IL7接收信号。通过观察T细胞在不同情况下的行为和功能，我们可以开始更好地理解这些因素是如何以及何时涉及控制T细胞数量的，以及它们如何出错导致疾病。

The Immune System plays a vital role in protecting individuals from parasitic infections by bacteria, viruses and other disease causing pathogens .T lymphocytes are immune cells that play a key role in regulating immune responses and having them in sufficient numbers is vital if they are to function properly. The number of T cells found in the immune system is carefully regulated by processes that control the production, survival and replication of T cells. Understanding how these processes work is important because when they go wrong, making too many T cells or the wrong type can cause autoimmune diseases such as diabetes or cause development of leukaemia or other cancers. Understanding how our bodies control T cell numbers are controlled also has clinical implications for developing treatments for conditions where T cell numbers are lost, for example in AIDS patients, for people undergoing cancer therapies which have the unwanted side affect of killing T cells or indeed for aiding reconstitution of bone transplant patients.All T cells express a surface protein, the T cell antigen receptor (TCR), that allows T cells to recognise and remember foreign pathogens. However, signals from this same receptor are also involved in controlling T cell survival and replication processes that are involved in controlling the size of the immune system. In addition, a soluble immune hormone, interleukin 7 (IL7) is also involved in regulating these same process and works together with TCR signals. The aim of our work is to gain a deeper understanding of how these two factors control the survival and replication of T cells. In order to do this, we have developed mouse models in which we can specifically control whether T cells receive signals from either the TCR or from IL7. By observing the behaviour and function of T cells in different situations, we can start to better understand how and when these factors are involved in controlling T cell numbers and how they can go wrong to cause disease.