Infection with human cytomegalovirus (HCMV) is thought to promote the expansion of low affinity, terminally differentiated HCMV-specific memory T cells with increasing age, thereby resulting in reduced vaccine responsiveness and poor responses to novel pathogens. This project sought to characterise and explore the relationship between the size of the HCMV-specific immune-response and general health in older age. A multi-parametric flow cytometry assay was used to characterise ex-vivo activation induced T cell responses against 19 immunogenic HCMV proteins in three groups of healthy volunteers aged between 18 to 85 years old. This approach is different to that utilised by most studies investigating the role of HCMV-specific immunity and ageing whereby focus is often limited to T cell responses against a few ‘dominant’ peptides, or proteins.
The response size against the 19 frequently recognized HCMV proteins were assessed by means of intracellular cytokine staining (ICS) assay based on these functional markers; CD40L, CD107a, TNFα, IFNγ, and IL-2. The memory phenotype with respect to each protein was also explored using these markers; CD45RA and CD27.
A significant increase in pp65-specific CD4+ T cells in the Oldest group was observed compared to the Young group. Also, a significant increase was observed in the size of the summated (sum of all protein-specific responses) CD8+ HCMV-specific T cell responses in the Older group compared to Young group, but no further increase was seen in the Oldest group indicating no further expansion with age.
Differences in levels of HCMV-specific T cell polyfunctionality was observed between target proteins, however level of polyfunctionality was neither reduced with increasing age nor in those with very large responses. In this study no significant differences were observed in the number of infections and health related problems reported by HCMV seropositive and seronegative aged individuals keeping a health diary; however, a significant trend was observed between the size of the summated HCMV-specific CD8+ T cells and the proportion of months unwell.
|Date of Award||Jan 2016|