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

急性和持续性病毒感染中细胞毒性 T 细胞群关闭的调节机制

• 批准号: nhmrc : 461263
• 负责人: Prof Gabrielle Belz
• 金额: $ 25.75万
• 依托单位: The Walter and Eliza Hall Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/mechanisms-regulating-shutdown-viral-infections/96781
• 关键词: Mechanisms; regulating; shutdown; cytotoxic; cell

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.

细胞凋亡，或程序性细胞死亡，是细胞死亡的一种形式，负责从体内清除多余或不需要的细胞。这是胚胎生长过程中组织重塑的基本机制，也是机体防止不需要的单个细胞类型生长的关键方式。以这种方式控制细胞生长是预防癌症的关键检查点。这种调节机制在确定稳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。两个蛋白家族在启动细胞凋亡过程中是必不可少的。一个被称为仅bh -3家族，而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，每个家族成员对不同类型的刺激作出反应，并在体内不同的组织中表达。到目前为止，只有一个bh3 -only家族成员BIM被确定为调节免疫反应的关闭。这一行为阻止了大量高攻击性细胞的产生，这些细胞是针对病原体的，无意中对身体造成了损害。这个控制检查点是正常的，但至关重要的，免疫反应的一部分。这些家族的其他成员也可能在这一过程中发挥重要作用，但他们的身份尚不清楚。本研究将确定BH-3-only和TNFR家族成员的哪些成员在(i)调节稳态淋巴细胞数量和（ii）在不同类型病原体感染中的关闭过程中发挥作用。这项工作将深入了解淋巴细胞是如何在静止动物和疾病中被调节的。