Dissecting the role of virus-specific T cells in providing protection against Marek's Disease Virus in chickens

马立克氏病病毒（MDV）感染导致鸡的淋巴瘤，并且每年给全球家禽业造成约15亿英镑的损失。每年约有220亿剂MDV疫苗用于控制肿瘤形成，但疫苗无法控制病毒复制，病毒继续进化并形成毒性越来越强的毒株。目前尚不清楚疫苗如何控制肿瘤形成，而无法控制病毒感染。了解疫苗失效的机制对于开发更有效的MDV疫苗至关重要。在动物模型研究中，已经表明T淋巴细胞通过产生炎性蛋白、细胞因子及其细胞毒性能力参与控制肿瘤形成和病毒感染。在此，我们的目的是（1）确定产生细胞因子的T淋巴细胞在控制接种鸡肿瘤形成中的作用（2）检查由MDV感染细胞产生的脂质介质PGE 2是否抑制感染鸡中T淋巴细胞的细胞毒性功能，这可能与疫苗诱导的T细胞反应控制感染失败有关。为了实现这些目标，我们将分析是否过继转移细胞因子产生T淋巴细胞从接种疫苗的鸡幼稚鸡可以控制肿瘤的形成。其次，我们将确定是否管理的化学抑制剂PGE2和疫苗接种病毒蛋白或过继转移的T淋巴细胞可以拯救T淋巴细胞的细胞毒性功能，从而保护鸡从肿瘤形成和病毒感染。

Infection with Marek's disease virus (MDV) causes lymphoma in chickens, and is responsible for annual losses of approximately £1.5 billion to the global poultry industry. Approximately 22 billion doses of MDV vaccine are annually used to control tumour formation, but the vaccine fails to control virus replication and the virus continues to evolve and form increasingly virulent strains. It is unknown how the vaccine can control tumour formation whilst failing to control viral infection. Understanding the mechanism(s) involved in vaccine failure is crucial for the development of more effective MDV vaccines.In animal model studies, it has been shown that T lymphocytes are involved in the control of tumour formation and viral infection via production of inflammatory proteins, cytokines, and their cytotoxic abilities. Here, we aim to (1) determine the role of cytokine producing T lymphocytes in the control of tumour formation in vaccinated chickens (2) examine whether a lipid mediator, PGE2, which is produced by MDV infected cells, suppresses cytotoxic function of T lymphocytes in the infected chickens, and this may be involved in the failure of vaccine-induced T cell responses to control infection. To achieve these objectives, we will analyse whether adoptive transfer of cytokine producing T lymphocytes from vaccinated chickens to naïve chickens can control tumour formation. Second, we will determine whether administration of chemical inhibitors of PGE2 and vaccination against viral proteins or adoptive transfer of T lymphocytes can rescue the cytotoxic function of T lymphocytes and thus protects the chickens from both tumour formation and viral infection.