Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence

Zanni, Franco; Vescovini, Rosanna; Biasini, Claudia; Fagnoni, Francesco; Zanlari, Luca; Telera, Anna Rita; Pede, Patricia Di; Passeri, Giovanni; Pedrazzoni, M.; Passeri, M; Franceschi, Claudio; Sansoni, Paolo

doi:10.1016/s0531-5565(03)00160-8

Cited by 195 publications

(154 citation statements)

References 32 publications

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“…It would appear that inflammaging is under genetic control and is detrimental for longevity (Chung et al, 2002;Franceschi et al, 2000;Zanni et al, 2003). This age-related chronic inflammatory activity, leading to long term tissue damage, is related to increased mortality risk from all causes in old persons.…”

Section: Immunosenescence and Inflammagingmentioning

confidence: 99%

“…These findings are consistent with age-associated thymic involution resulting in reduced numbers of "virgin" naive T cells produced (Figure 2). Overall, changes in T cell effector function and repertoire are contributing factors in the age-associated decline of immunity to pathogen challenge and vaccination and increased predisposition to cancer (Hakim and Gress, 2007 (Zanni et al, 2003). Thus, virus-specific memory CD8 + T cells have impaired proliferation and IL-2 production (Effros and Walford, 1983).…”

Section: Naïve and Memory T Cells In Agingmentioning

confidence: 99%

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Nutrition, diet and immunosenescence

Maijó

Clements

Ivory

et al. 2014

Mechanisms of Ageing and Development

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Ageing is characterized by immunosenescence and the progressive decline in immunity in association with an increased frequency of infections and chronic disease. This complex process affects both the innate and adaptive immune systems with a progressive decline in most immune cell populations and defects in activation resulting in loss of function. Although host genetics and environmental factors, such as stress, exercise and diet can impact on the onset or course of immunosenescence, the mechanisms involved are largely unknown. This review focusses on identifying the most significant aspects of immunosenescence and on the evidence that nutritional intervention might delay this process, and consequently improve the quality of life of the elderly. We would like to thank the reviewers for their careful review of our manuscript, which has been revised accordingly. Below, we have provided a point-by-point reply to the issues raised: AbstractAgeing is characterized by immunosenescence and the progressive decline in immunity in association with an increased frequency of infections and chronic disease. This complex process affects both the innate and adaptive immune systems with a progressive decline in most immune cell populations and defects in activation resulting in loss of function. Although host genetics and environmental factors, such as stress, exercise and diet can impact on the onset or course of immunosenescence, the mechanisms involved are largely unknown. This review focusses on identifying the most significant aspects of immunosenescence and on the evidence that nutritional intervention might delay this process, and consequently improve the quality of life of the elderly.

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Section: Immunosenescence and Inflammagingmentioning

confidence: 99%

Section: Naïve and Memory T Cells In Agingmentioning

confidence: 99%

Nutrition, diet and immunosenescence

Maijó

Clements

Ivory

et al. 2014

Mechanisms of Ageing and Development

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“…Some evidence-including a decrease in naive T cell, accumulation of memory T cells, loss of CD28 costimulatory signal, increased number of CD8 ϩ T cells producing IFN-␥, and increased levels of proinflammatory cytokines-indicate that a peculiar activation of the immune system accompanies the aging process in humans (1)(2)(3)(4)(5)(6). However, the basic mechanisms underlying this chronic inflammatory status in aged humans, we proposed to call inflamm-aging (7), are still elusive.…”

mentioning

confidence: 99%

Massive Load of Functional Effector CD4+ and CD8+ T Cells against Cytomegalovirus in Very Old Subjects

Vescovini

Biasini

Fagnoni³

et al. 2007

The Journal of Immunology

153

111

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A progressive, systemic, and low-grade proinflammatory status is one of the major characteristics of immunosenescence. Emerging data suggest a possible contribution of CMV, known to chronically infect a large proportion of humans, lifelong from newborns to centenarians. To test this hypothesis, we evaluated functional T cell responses to two CMV immunogenic proteins, pp65 and IE-1, in 65 chronically infected subjects aged 25–100 years. PBMC were stimulated with mixtures of peptides spanning the entire sequence of both proteins, and Ag specificity and magnitude of intracellular IFN-γ- and TNF-α-positive cells were then analyzed within both CD4+ and CD8+ T cells. Results indicate that pp65 and, to a lesser extent, IE-1 constitute major Ags against which aged people target functionally efficient T cell effector responses with massive production of Th1 cytokines and exhibition of CD107a degranulation marker. As a result, the production of IFN-γ induced in T cells by both Ags was seven to eight times greater in very old than in young subjects. The comparative analysis of pp65-specific responses in these very long-term carriers revealed a reciprocal relationship between CD4+ and CD8+ producing IFN-γ in the same individuals. These results indicate that CMV represents an important pathogen responsible for a strong immune activation in human aging. Such a remarkable burden of effector CD4+ and CD8+ T cells may be necessary to protect the elderly from CMV endogenous reactivation, but can turn detrimental by giving a substantial contribution to the proinflammatory status that accompanies the main age-related diseases.

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“…CD8 ϩ CD28 Ϫ effector T cells have mainly been attributed detrimental effects in old age. Their accumulation has been reported to trigger chronic inflammatory processes in elderly persons (9,10). High numbers of CD8 ϩ CD28 Ϫ cells have also been shown to be associated with insufficient efficacy of vaccines to induce Ab production in old age (8,11) and to predict higher mortality (12).…”

mentioning

confidence: 99%

CD25-Expressing CD8+ T Cells Are Potent Memory Cells in Old Age

Herndler‐Brandstetter¹,

Schwaiger²,

Veel³

et al. 2005

The Journal of Immunology

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We have recently described an IL-2/IL-4-producing CD8+CD25+ nonregulatory memory T cell population that occurs in a subgroup of healthy elderly persons who characteristically still have a good humoral response after vaccination. The present study addresses this specific T cell subset and investigates its origin, clonal composition, Ag specificity, and replicative history. We demonstrate that CD8+CD25+ memory T cells frequently exhibit a CD4+CD8+ double-positive phenotype. The expression of the CD8 αβ molecule and the occurrence of signal-joint TCR rearrangement excision circles suggest a thymic origin of these cells. They also have longer telomeres than their CD8+CD25− memory counterparts, thus indicating a shorter replicative history. CD8+CD25+ memory T cells display a polyclonal TCR repertoire and respond to IL-2 as well as to a panel of different Ags, whereas the CD8+CD25− memory T cell population has a more restricted TCR diversity, responds to fewer Ags, and does not proliferate in response to stimulation with IL-2. Molecular tracking of specific clones with clonotypic primers reveals that the same clones occur in CD8+CD25+ and CD8+CD25− memory T cell populations, demonstrating a lineage relationship between CD25+ and CD25− memory CD8+ T cells. Our results suggest that CD25-expressing memory T cells represent an early stage in the differentiation of CD8+ cells. Accumulation of these cells in elderly persons appears to be a prerequisite of intact immune responsiveness in the absence of naive T cells in old age.

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Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence

Cited by 195 publications

References 32 publications

Nutrition, diet and immunosenescence

Nutrition, diet and immunosenescence

Massive Load of Functional Effector CD4+ and CD8+ T Cells against Cytomegalovirus in Very Old Subjects

CD25-Expressing CD8+ T Cells Are Potent Memory Cells in Old Age

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