Diverse specificity, phenotype and anti-viral activity of cytomegalovirus specific CD8+ T cells
Journal of Virology
American Society for Microbiology
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Jackson, S., Mason, G., Okecha, G., Sisson, J., & Wills, M. (2014). Diverse specificity, phenotype and anti-viral activity of cytomegalovirus specific CD8+ T cells. Journal of Virology https://doi.org/10.1128/JVI.01477-14
CD8+ T cells specific for pp65, IE1 and IE2 are present at high frequencies in HCMV seropositive individuals and these have been shown to have phenotypes associated with terminal differentiation, as well as both cytokine and proliferative dysfunctions, especially in the elderly. However, more recently, T cell responses to many other HCMV proteins have been described but little is known about their phenotype and function. Consequently, in this study, we chose to determine the diversity of HCMV specific CD8+ T cell responses to eleven HCMV ORFs in a cohort of donors aged 20 – 80 years old as well as their ability to secrete IFNγ. Finally, we also tested their functional anti-viral capacity using a novel viral dissemination assay. We identified substantial CD8+ T cell responses by IFNγ ELISPOT assays to all eleven of these HCMV proteins and, across the cohort, individuals displayed a range of responses from the tightly focused to highly diverse which were stable over time. CD8+ T cell responses to the HCMV ORFs were highly differentiated and predominantly CD45RA+, CD57+ and CD28-, across the cohort. These highly differentiated cells had the ability to inhibit viral spread even following direct ex-vivo isolation. Taken together, our data argue that HCMV specific CD8+ T cells have effective anti-viral activity irrespective of the viral protein recognized across the whole cohort and despite viral immune evasion. IMPORTANCE Human cytomegalovirus (HCMV) is normally carried without clinical symptoms and is widely prevalent in the population, however, it often causes severe clinical disease in individuals with compromised immune responses. HCMV is never cleared after primary infection but persists in the host for life. In HCMV carriers, the immune response to HCMV includes large numbers of virus-specific immune cells and the virus has evolved many mechanisms to evade the immune response. While this immune response seems to protect healthy people from subsequent disease the virus is never eliminated. It has been suggested that this continuous surveillance by the immune system may have deleterious effects in later life. The data presented in this paper examines immune responses from a cohort of donors and shows that these immune cells are effective at controlling the virus and can overcome the viruses lytic cycle immunevasion mechanisms.
This work was funded by British Medical Research Council Grant G0701279 and supported by the NIHR Cambridge BRC Cell Phenotyping hub.
External DOI: https://doi.org/10.1128/JVI.01477-14
This record's URL: https://www.repository.cam.ac.uk/handle/1810/245589
Attribution-NonCommercial 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by-nc/2.0/uk/
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