Mechanisms regulating the shutdown of cytotoxic T cell populations in acute and persistent viral infections

细胞凋亡，或程序性细胞死亡，是细胞死亡的一种形式，负责将不需要的或多余的细胞从体内移除。这是胚胎发育过程中允许组织重塑的基本机制，也是人体防止个别细胞类型不必要的生长的关键方式。以这种方式控制细胞生长是预防癌症的关键关卡。这一调节机制在确定稳定状态和免疫反应后产生的免疫细胞的数量和类型方面也很重要。两个蛋白质家族在启动这一细胞凋亡过程中起着至关重要的作用。一个是BH-3-Only家族，另一个是肿瘤坏死受体(TNFR)家族。这些家族由几个家族成员组成，每个成员对不同类型的刺激做出反应，并在体内不同的组织中表达。到目前为止，只有一个BH-3家族成员BIM被确定为调节免疫反应的关闭。这一行动可以防止大量针对病原体的高度侵略性细胞的产生，这些细胞无意中对身体造成了损害。这一控制检查点是免疫反应的正常但至关重要的一部分。这些家庭的其他成员也可能在这一进程中发挥重要作用，但他们的身份尚不清楚。这项研究将确定BH-3-Only和TNFR家族成员中的哪些成员在(I)调节处于稳定状态的淋巴细胞数量，以及(Ii)在不同类型病原体感染的关闭过程中发挥作用。这项工作将为深入了解淋巴细胞是如何在休息的动物和疾病中调节的。

Apoptosis, or programmed cell death, is the form of cell death responsible for removal of unwanted or excess cells from the body. This is an essential mechanism to allow remodelling of tissues as an embryo grows and is a crucial way in which the body prevents the unwanted outgrowth of individual cell types. Control of cell growth in this way is a key checkpoint in preventing cancers. This regulatory mechanism is also important in determining the number and type of immune cells that are generated at steady state and following an immune response. Two families of proteins are essential in initiating this process of apoptosis. One is known as the BH-3-only family, while the other is the tumour-necrosis receptor (TNFR) family. These families are made up of several family members, each of which responds to different types of stimuli, and are expressed in different tissues in the body. So far only one BH-3-only family member, BIM, has been identified to regulate shut-down of an immune response. This action prevents the generation of large numbers of highly aggressive cells that are specific for a pathogen inadvertently causing damage to the body. This control checkpoint is a normal, but vital, part of the immune response. Other members of these families are also likely to play an important role in this process, but as yet their identity is unknown. This study will determine which members of the BH-3-only and TNFR family members play a role in (i) regulating the numbers of lymphocytes present at steady state, and (ii) in the shut-down process in different types of pathogen infection. This work will provide insight into how lymphocytes are regulated in the resting animal, and in disease.