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

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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.