The Role of Chicken Gamma Delta T Cells in Immunity Against Marek’s Disease Virus

Abstract

Gamma delta (γδ) T cells play key biological functions in immunity against pathogens and tumors in many species. γδ T cells recognize various antigens via their T cell receptor (TCR), natural killer (NK) receptors, and pattern recognition receptors (PRRs). These cells produce cytokines and release cytotoxic granules in mammals whereas the activation mechanisms of chicken γδ T cells have not been elucidated. In chickens, the involvement of γδ T cells in immunity against Marek’s disease virus (MDV) infection has been suggested. Marek’s disease (MD) is a malignant lymphomatous disease of chickens caused by MDV. Due to its highly cell-associated feature, cell-mediated immunity is believed to be critical for protection against MDV replication, dissemination, and tumor formation. Although an increase in interferon (IFN)-γ- or interleukin (IL)-10-expressing γδ T cells in MDV-challenged chickens has been observed, detailed functions of these cells in MDV immunity or pathogenesis have remained underexplored. Therefore, the aims of the studies presented in this thesis were to examine activation mechanisms of γδ T cells and their functional roles in immunity against MDV. Our studies revealed that Cytosine-phosphate-Guanine-Oligodeoxynucleotide (CpG-ODN) 2007 induced IFN-γ secretion by TCR-stimulated γδ T cells. Further, the results of splenocyte or sorted γδ T cell culture in presence of Polyriboinosinic polyribocytidylic acid (poly(I:C)) suggested that IFN-γ production by poly(I:C)-stimulated γδ T cells requires other signals from non-γδ T cells. Subsequently, γδ T cells were characterized in MDV-vaccinated and -challenged chickens. The involvement of γδ T cells producing IFN-γ and transforming growth factor (TGF)-β in immunity conferred by MDV vaccines was suggested. Further, the role of IFN-γ-producing γδ T cells in immunity against MDV infection was evaluated and these cells were shown to contribute to immunity against MD. Lastly, the effect of the tumor microenvironment (TME) on γδ T cells was investigated. The results suggested that activated γδ T cells including IFN-γ-producing splenic γδ T cells are suppressed in the TME generated by MDV. Overall, the studies in this thesis demonstrate activation mechanisms of chicken γδ T cells and their involvement in protective immunity against MDV.