Healthy Aging and Latent Infection with CMV Lead to Distinct Changes in CD8 + and CD4 + T-Cell Subsets in the Elderly (original) (raw)
Related papers
Immunity & Ageing Effect of ageing on CMV-specific CD8 T cells from CMV seropositive healthy donors
Background: Ageing is associated with changes in the immune system with substantial alterations in T-lymphocyte subsets. Cytomegalovirus (CMV) is one of the factors that affect functionality of T cells and the differentiation and large expansions of CMV pp65-specific T cells have been associated with impaired responses to other immune challenges. Moreover, the presence of clonal expansions of CMV-specific T cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious diseases in the elderly. In this study, we analyse the effect of ageing on the phenotype and frequency of CMV pp65-specific CD8 T cell subsets according to the expression of CCR7, CD45RA, CD27, CD28, CD244 and CD85j.
Functional Changes of T-Cell Subsets with Age and CMV Infection
International Journal of Molecular Sciences
Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57− T-cells regardless of age. CMV-seronegative individuals have no or a very low percentage...
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.
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.
Mechanisms of Ageing and Development, 2001
Results from the previous times (Times 1 -3) of the Swedish longitudinal OCTO immune study indicated that a combination of high CD8 and low CD4 percentages and poor T-cell proliferation in PBL was associated with a higher 2-year mortality in a sample of very old Swedish individuals. The combination of immune parameters was closely related to an inverted CD4/CD8 ratio. In the present study at Time 4 (T4) results are reported from the final follow-up of this longitudinal study, 8 years after it was initiated in 1989. An additional goal at this time point was to examine the immune system alterations in the very old in relation to evidence of lymphocyte activation and cytomegalovirus antibody status. In the present study immune system changes were identified that suggest a loss of T-cell www.elsevier.com/locate/mechagedev -* Corresponding author. : S 0 0 4 7 -6 3 7 4 ( 0 0 ) 0 0 2 1 0 -4 J. Olsson et al. / Mechanisms of Ageing and De6elopment 121 (2000) 187-201 188
Effect of ageing on CMV-specific CD8 T cells from CMV seropositive healthy donors
Immunity & Ageing, 2009
BACKGROUND: Ageing is associated with changes in the immune system with substantial alterations in T-lymphocyte subsets. Cytomegalovirus (CMV) is one of the factors that affect functionality of T cells and the differentiation and large expansions of CMV pp65-specific T cells have been associated with impaired responses to other immune challenges. Moreover, the presence of clonal expansions of CMV-specific T cells
Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly
Experimental Gerontology, 2004
Large clonal expansions of peripheral CD8 þ T cells carrying receptors for single epitopes of CMV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. To study the effect of ageing on the ability of CMV-specific CD8 þ T cells to produce type 1-and type 2-cytokines, interferon-g-and IL-10-producing, CD8 þ T cell responses in the presence of CMV peptide antigen were measured in CMV-seropositive old and young donors. We found that large expansions of A2/NLV-specific CD8 þ T lymphocytes in the elderly are accompanied by a partial loss of antigen responsiveness as reflected in a greatly decreased frequency of antigen-specific IFN-gand IL-10-producing cells. Thus, despite carrying specific antigen receptors, the majority of the clonally expanded CMV-specific CD8 þ cells in the elderly was dysfunctional according to these criteria. Our data indicated a bias towards a more anti-inflammatory response in the elderly. The accumulation of dysfunctional CMV-specific cells might fill the 'immunological space' and decrease the available repertoire of T cells for novel antigens. This might account for the increased incidence of many infectious diseases in the elderly. q