Defining a role for TRAIL in the regulation of the immune response to MCMV infection

Iona Schuster

Research output: ThesisDoctoral Thesis

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[Truncated] The immune system is a complex network of cells and signalling molecules distributed throughout the body that acts to control pathogens and transformed cells. Human cytomegalovirus (HCMV) is a pathogen that establishes a life-long infection and is controlled by a functional immune system. However, in individuals with impaired immunity, primary HCMV infection or reactivation of latent HCMV can lead to a number of life-threatening diseases. A prerequisite for the successful treatment of HCMV infection is the understanding of the processes leading to a robust and protective immune response. As HCMV is a species-specific virus, murine cytomegalovirus (MCMV) infection of its natural host, the mouse, is an ideal model for the investigation of immune mechanisms limiting CMV infection in vivo.
Similar to HCMV, MCMV replicates to high viral titres in the salivary gland and virus is shed into the saliva, thus leading to horizontal transmission of the virus. Previous work has established that CD4+ T cells are central to limiting MCMV replication in the salivary gland, however, the mechanisms by which CD4+ T cells control viral replication have not been defined. Here, I have assessed the dynamics of T cell activation and effector responses over the course of MCMV and determined that CD4+ T cells accumulating in the salivary gland are highly activated and gain cytotoxic function. Even though CD4+ T cells also produce high levels of IFN-γ and TNF-α, these cytokines do not seem to contribute to viral control as blocking of IFN-γ or TNF-α did not impact on MCMV titres in the salivary gland. Notably, MCMV infection induces the expression of MHC II in the salivary gland, suggesting a direct role for CD4+ T cells in limiting MCMV infection in this tissue.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2012


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