Role of T cell subsets in Marek’s disease virus pathogenesis

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Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes paralysis, immunosuppression and deadly lymphomas. MDV-induced lymphomas are considered to be the most prevalent clinically-diagnosed cancer in animals and the virus causes substantial economic losses in poultry industry worldwide. In susceptible chickens, MDV infection can cause mortality of up to 100%, depending on the genetic background of the host and the virulence of the virus strain. Even though current MDV vaccines are highly effective in minimizing commercial losses due to tumor formation, they do not elicit sterilizing immunity, allowing a continued evolution of MDV strains in vaccinated chickens. Since the advent of widespread vaccination, there has been a continuous increase in the virulence of MDV field strains. These more virulent strains are able to overcome vaccine protection and pose a serious threat to poultry production. Therefore, we need a better understanding of MDV pathogenesis and vaccine responses in chickens to develop more potent vaccines that control this deadly pathogen.Despite many years of research, the role of T cell subsets in MDV pathogenesis and vaccine protection remains poorly understood, mostly due to the lack of reverse genetics in chickens. The aim of work package 6 (WP6) is i) to determine the role of γδ T cells in MDV infection, ii) to assess if they are important for vaccine protection and iii) to investigate if MDV pathogenesis is dependent on the presence of αβ T cells. To address these aims, we will use αβ and γδ T cell knockout chickens in combination with molecular and immunological methods. The proposed experiments will not only shed light on the role of these T cell subsets in MDV pathogenesis and vaccine protection but also expand the knowledge on the life cycle of this highly oncogenic virus.The individual research projects within FOR5130 benefit from the collaborations among each other and provide a better insight into the immune system of chickens in relation to important pathogens.