Role of CMV in immune senescence (original) (raw)
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The Contribution of Cytomegalovirus Infection to Immune Senescence Is Set by the Infectious Dose
Frontiers in immunology, 2017
The relationship between human cytomegalovirus (HCMV) infections and accelerated immune senescence is controversial. Whereas some studies reported a CMV-associated impaired capacity to control heterologous infections at old age, other studies could not confirm this. We hypothesized that these discrepancies might relate to the variability in the infectious dose of CMV occurring in real life. Here, we investigated the influence of persistent CMV infection on immune perturbations and specifically addressed the role of the infectious dose on the contribution of CMV to accelerated immune senescence. We show in experimental mouse models that the degree of mouse CMV (MCMV)-specific memory CD8 T cell accumulation and the phenotypic T cell profile are directly influenced by the infectious dose, and data on HCMV-specific T cells indicate a similar connection. Detailed cluster analysis of the memory CD8 T cell development showed that high-dose infection causes a differentiation pathway that pr...
Clinical and Vaccine Immunology, 2010
T cells are strongly affected by immune aging, a phenomenon that leads to increased susceptibility to infections and decreased vaccination efficacy in elderly individuals. Cytomegalovirus (CMV) infection induces vigorous T-cell immune responses in humans and is thought to be a driving force of immune aging. In the present study we analyzed CMV-induced quantitative and qualitative differences in the cytokine-expressing T-cell repertoire from individuals of different age groups after in vitro stimulation. The CMV pp65 peptide pool and the superantigen Staphylococcus enterotoxin B (SEB) induced higher proportions of CD8 ؉ effector T cells expressing gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), and granulocyte-macrophage colony-stimulating factor in the oldest study group, while only SEB induced increased responses in the middle-aged study group. Notably, CMV-specific multiple cytokine expression patterns revealed higher proportions of IFN-␥-and TNF-␣-coexpressing CD8 ؉ T cells exclusively in the oldest study group. These qualitative differences were absent in SEB-induced CD8 ؉ effector T cells, although quantitative differences were detected. We report age-dependent qualitative changes in CMV-specific CD8 ؉ T-cell cytokine patterns which are biocandidate markers of immune exhaustion in elderly individuals.
Role of persistent CMV infection in configuring T cell immunity in the elderly
Immunity & Ageing, 2007
Ageing is associated with declines in many physiological parameters, including multiple immune system functions. The rate of acceleration of the frequency of death due to cardiovascular disease or cancer seems to increase with age from middle age up to around 80 years, plateauing thereafter. Mortality due to infectious disease, however, does not plateau, but continues to accelerate indefinitely. The elderly commonly possess oligoclonal expansions of T cells, especially of CD8 cells, which, surprisingly, are often associated with cytomegalovirus (CMV) seropositivity. This in turn is associated with many of the same phenotypic and functional alterations to T cell immunity that have been suggested as biomarkers of immune system aging. Thus, the manner in which CMV and the host immune system interact is critical in determining the "age" of specific immunity. We may therefore consider immunosenescence in some respects as an infectious state. This implies that interventions aimed at the pathogen may improve the organ system affected. Hence, CMV-directed anti-virals or vaccination may have beneficial effects on immunity in later life.
Differential Impact of Age and Cytomegalovirus Infection on the T Cell Compartment
The Journal of Immunology, 2013
γδ T cells represent a subset of unconventional T lymphocytes that are known for their reactivity against different pathogens and considered as intermediate mediators between adaptive and innate immunity. We provide in this paper further insights underlying the changes that affect the γδ T cell compartment with advanced age in humans. We show that both aging and CMV infection impact independently on the γδ T cell compartment. Most γδ T cells are significantly affected by age and present a decreased frequency in the elderly. The decline of the γδ T cell pool appears to be independent from the activity of the thymus, arguing in favor of an extrathymic site of γδ T cell production in humans. Of note, CMV infection, which is directly associated with the activation of the pool of Vδ2(-) γδ T cells, promotes nonetheless the inflation of this compartment throughout life. CMV seropositivity accentuates further the accumulation of highly differentiated lymphocytes in Vδ2(-) γδ T cell subsets with time, in contrast to Vδ2(+) γδ T cells, which maintain a less differentiated phenotype. This is similar to the effect of CMV on αβ T cells and suggests that γδ T cells may vary in differentiation phenotype according to distinct stimuli or pathogens.
Frontiers in immunology, 2017
Immunosenescence is a progressive deterioration of the immune system with aging. It affects both innate and adaptive immunity limiting the response to pathogens and to vaccines. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, and its persistent infection results in functional and phenotypic changes to the T-cell repertoire, the aim of this study was to analyze the effect of CMV-seropositivity and aging on the expression of CD300a and CD161 inhibitory receptors, along with the expression of CD57 marker on CD4(+), CD8(+), CD8(+)CD56(+) (NKT-Like) and CD4(-)CD8(-) (DN) T-cell subsets. Our results showed that, regardless of the T-cell subset, CD57(-)CD161(-)CD300a(+) T-cells expand with age in CMV-seropositive individuals, whereas CD57(-)CD161(+)CD300a(+) T-cells decrease. Similarly, CD57(+)CD161(-)CD300a(+) T-cells expand with age in CMV-seropositive individuals in all subsets except in DN cells and CD57(-)CD161(+)CD300a(-) T-...