Characterisation of T cell responses to proteins expressed during Human Cytomegalovirus latency
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Human cytomegalovirus (HCMV) is a betaherpesvirus that establishes a lifelong infection in hosts. In the majority of cases, the immune response to primary HCMV infection limits viral replication and dissemination, such that overt clinical disease is prevented. However, the immune system cannot prevent the virus establishing a latent infection, which enables lifelong persistence. Historically, a long-standing view was that viral gene expression during latency was largely absent, thus facilitating the avoidance of immune detection. However, it has now been established that viral activity in latency is far from quiescent, and the expression of a number of viral genes is known to occur. Therefore, an important question arises: are T cells specific to these proteins generated, and, if so, why are HCMV latently infected cells maintained in the face of these potential T cell responses? Previous work has shown that two such viral gene products, UL138 and LUNA, are recognised by CD4+ T cells, with a subpopulation of these cells secreting the immunosuppressive cytokines interleukin (IL)-10 and transforming growth factor beta (
Using overlapping peptide pools designed to cover the whole of the predicted amino acid sequence of these HCMV proteins, in combination with fluorescent ELIspot (FluoroSpot), ELISA, and intracellular cytokine staining, I have determined the frequency, cytokine secretion profile, effector function, and memory phenotype of CD4+ and CD8+ T cells in a large cohort of HCMV seropositive healthy donors. My results show that these viral gene products are also recognised by CD4+ T cells and are composed of distinct cellular populations secreting either IFN
Given that latency-specific IL-10 secreting T cells were found to be a separate population to those secreting IFN