CMV Latent Infection Improves CD8+ T Response to SEB Due to Expansion of Polyfunctional CD57+ Cells in Young Individuals

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.

Cytomegalovirus and HIV: A Dangerous Pas de Deux

“…The effects of CMV infection on host immunity are not always deleterious, and CMV might have a beneficial effect on the immune system by providing immune protection against other pathogens (so-called heterologous immunity [40]) in younger healthy people. This could explain why humans (and many other species) tolerate the very high prevalence of this infection, and it is consistent with the notion of antagonistic pleiotropy [41][42][43]. Certain biological features can be selected as favorable during youth but become harmful with age (ie, during a stage of life that is neutral in terms of evolutionary selection) [44].…”

How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?

“…CMV seropositivity has also been shown to induce the expansion of polyfunctional CD8+ T cells (CD8+CD57+) secreting multiple cytokines (IFN-γ, TNF-α), which can degranulate in response to stimulation, and are therefore crucial for the generation of optimal responses to infections and vaccines (Pera et al 2014). The authors of this study have suggested that CMV seropositivity may provide protection against some pathogens by keeping the immune system in a state of alert.…”

Identification of human cytomegalovirus in tumour tissues of colorectal cancer and its association with the outcome of non-elderly patients

“…In the elderly, chronic latent HCMV infection increases the mortality rate, which could be attributed to HCMV-induced immunosenescence with decreased immunity to microbes and cancers (Pawelec et al, 2010;Sansoni et al, 2014;Savva et al, 2013). In the non-elderly, on the other hand, chronic HCMV infection may actually be beneficial in that it augments the T-cell immunity and has been associated with a reduced cancer risk in transplant patients (Couzi et al, 2010;Furman et al, 2015;Pera et al, 2014). In this study, significant intra-tumoural inflammatory responses were more frequently observed in HCMVpositive tumours, suggesting that viral replication may activate the immune response in the tumour microenvironment and contribute to a favourable prognosis (Naito et al, 1998).…”