Abstract
Cytomegalovirus (CMV) latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality) rather than with quantity (percentage of T cells). We analyze the effect of CMV infection on CD8+ T cells polyfunctionality ―degranulation (CD107a), IFN-gamma and TNF-alpha production―, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB). Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57− cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a) is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells producing pro-inflammatory cytokines. These findings highlight the necessity of further studies on the benefits/detrimental effects of CMV infection in the response to vaccination and other infections.
Highlights
CMV chronic infection has a high prevalence that varies worldwide
The analysis of the frequency of Staphylococcal Enterotoxin B (SEB)-responding CD8+ T cells, considered as those capable of any kind of response (CD107a, IFN-gamma, TNF-alpha), showed that the percentage of SEB-responding CD8+ T cells is higher in middle age CMVseropositive individuals compared to young individuals, both CMV-seropositive and CMV-seronegative
The results showed a significant increase of CD8+CD57+ T cell subset in young and middle age CMVseropositive individuals compared to young CMV-seronegative
Summary
CMV chronic infection has a high prevalence that varies worldwide. Seropositivity is related to geographic, ethnic and social factors and increases with age [1]. CMV-seropositivity is associated with an increased risk of death and cardiovascular diseases [8,9,10] and with the development of an ‘‘Immune Risk Phenotype’’ (IRP), predictive of early mortality in the elderly [11,12,13]. CMV is considered a major driving force of immunosenescence characterized by the accumulation of antigen-specific, oligoclonally expanded CD8+CD28– CD57+ T cells. These cells have been proposed as terminally differentiated, senescent, dysfunctional, effector-memory T lymphocytes that have gone through several rounds of cell divisions (for review see [14,15])
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