Healthy Aging and Latent Infection with CMV Lead to Distinct Changes in CD8+ and CD4+ T-Cell Subsets in the Elderly

Weinberger, Birgit; Lazuardi, Lutfan; Weiskirchner, Ilka; Keller, Michael; Neuner, Christoph; Fischer, Karl-Heinz; Neuman, Ber; Würzner, Reinhard; Grubeck‐Loebenstein, Beatrix

doi:10.1016/j.humimm.2006.10.019

Cited by 122 publications

(103 citation statements)

References 23 publications

(24 reference statements)

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“…CMV is associated with global changes to the host's immune profile, which are particularly well documented in the peripheral T lymphoid pool (van de Berg et al 2008), being associated with lymphocyte phenotype alterations very similar to those published as ageassociated (Weinberger et al 2007). Proinflammatory cytokines have been substantially implicated in these age-and CMV-related alterations to T-cell immunity.…”

Section: Cd8mentioning

confidence: 88%

The role of the T cell in age-related inflammation

Macaulay

Akbar

Henson

2012

AGE

103

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Ageing is accompanied by alterations to T-cell immunity and also by a low-grade chronic inflammatory state termed inflammaging. The significance of these phenomena is highlighted by their being predictors of earlier mortality. We have recently published that the proinflammatory cytokine TNFα is a strong inducer of CD4 + T-cell senescence and T-cell differentiation, adding to the growing body of literature implicating proinflammatory molecules in mediating these critical age-related T-cell alterations. Moreover, the inflammatory process is also being increasingly implicated in the pathogenesis of many common and severe age-related diseases, including cancer, cardiovascular diseases and type 2 diabetes. Furthermore, major age-related risk factors for poor health, such as obesity, stress and smoking, are also associated with an upregulation in systemic inflammatory markers. We propose the idea that the ensuing inflammatory response to influenza infection propagates cardiovascular diseases and constitutes a major cause of influenzarelated mortality. While inflammation is not a negative phenomenon per se, this age-related dysregulation of inflammatory responses may play crucial roles driving age-related pathologies, T-cell immunosenescence and CMV reactivation, thereby underpinning key features of the ageing process.

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Section: Cd8mentioning

confidence: 88%

The role of the T cell in age-related inflammation

Macaulay

Akbar

Henson

2012

AGE

103

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“…These late‐differentiated CD8 + T cells possess many features of replicative senescence that have been characterized in long‐term in vitro cultures (Signer et al ., 2008). Although CD4 + T cells are more resistant to age‐related phenotypic and functional changes than CD8 + T cells (Weinberger et al ., 2007), a progressive increase in the percentage of senescence‐like CD4 + T cells is common with increasing age in healthy individuals (Goronzy et al ., 2007; Czesnikiewicz‐Guzik et al ., 2008). This increase in senescence‐like CD4 + T cells is also observed in patients with chronic infections (Fletcher et al ., 2005) and autoimmune diseases such as rheumatoid arthritis (RA) (Goronzy et al ., 2005).…”

Section: Cellular Senescence and Immune Cell Fate Decisionmentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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SummaryCellular senescence occurs not only in cultured fibroblasts, but also in undifferentiated and specialized cells from various tissues of all ages, in vitro and in vivo. Here, we review recent findings on the role of cellular senescence in immune cell fate decisions in macrophage polarization, natural killer cell phenotype, and following T‐lymphocyte activation. We also introduce the involvement of the onset of cellular senescence in some immune responses including T‐helper lymphocyte‐dependent tissue homeostatic functions and T‐regulatory cell‐dependent suppressive mechanisms. Altogether, these data propose that cellular senescence plays a wide‐reaching role as a homeostatic orchestrator.

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“…They also show a series of alterations that lead to a state of clonal exhaustion or replicative senescence, characterized by phenotypic and functional changes (12,18,22,43,49), which in turn lead to decreased levels of secretion of gamma interferon (2,37,38,42), perforin, and granzymes, making them more inefficient for cytotoxicity than CD45RA ϩ cells (4,54). In addition, these exhausted clones resemble in some aspects the senescent clones that naturally accumulate throughout aging (5,29,47,50), and age and latent HCMV infection seem to induce similar changes in the T-cell pool (51). Further studies are therefore necessary to clarify this aspect in transplant patients with prior HCMV replication.…”

Section: Vol 16 2009 Cd8 T Cells and Cytomegalovirus Replication 1435mentioning

confidence: 99%

Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8⁺T Cells and Cytomegalovirus Replication after Transplantation

Cantisán

Torre‐Cisneros²,

Lara

et al. 2009

Clin Vaccine Immunol

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In this cross-sectional study of 42 solid organ transplant recipients, the association of human cytomegalovirus (HCMV) replication and age with the phenotype of the HCMV-specific CD8 ؉ T cells was analyzed by using the CMV pp65 HLA-A*0201 pentamer. A correlation between the proportion of CD28 ؊ HCMV-specific CD8 ؉ T cells and age was observed in patients without HCMV replication (r ‫؍‬ 0.50; P ‫؍‬ 0.02) but not in patients with HCMV replication (r ‫؍‬ ؊0.05; P ‫؍‬ 0.83), a finding which differs from that observed for total CD8 ؉ T cells. Within the group of patients younger than 50 years of age, patients with HCVM replication after transplantation had higher percentages of CD28 ؊ HCMV-specific CD8 ؉ T cells (85.6 compared with 58.7% for patients without HCMV replication; P ‫؍‬ 0.004) and CD27؊ HCMV-specific CD8 ؉ T cells (90.7 compared with 68.8% for patients without HCMV replication; P ‫؍‬ 0.03). However, in patients older than age 50 years, a high frequency of these two subpopulations was observed in patients both with and without previous HCMV replication (for CD28 ؊ HCMVspecific CD8 ؉ T cells, 84.4 and 80.9%, respectively [P ‫؍‬ 0.39]; for CD27 ؊ HCMV-specific CD8 ؉ T cells 86.6 and 81.5%, respectively [P ‫؍‬ 0.16]). In conclusion, the present study shows that in the group of recipients younger than age 50 years, HCMV replication after transplantation is associated with a high percentage of CD27 ؊ and CD28 ؊ HCMV-specific CD8 ؉ T cells. These results suggest that the increased percentage of CD27 ؊ or CD28 ؊ HCMVspecific subsets can be considered a biomarker of HCMV replication in solid organ transplant recipients younger than age 50 years but not in older patients. Further studies are necessary to define the significance of these changes in HCMV-associated clinical complications posttransplantation.

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Healthy Aging and Latent Infection with CMV Lead to Distinct Changes in CD8+ and CD4+ T-Cell Subsets in the Elderly

Cited by 122 publications

References 23 publications

The role of the T cell in age-related inflammation

The role of the T cell in age-related inflammation

Cellular senescence impact on immune cell fate and function

Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8⁺T Cells and Cytomegalovirus Replication after Transplantation

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Healthy Aging and Latent Infection with CMV Lead to Distinct Changes in CD8+ and CD4+ T-Cell Subsets in the Elderly

Cited by 122 publications

References 23 publications

The role of the T cell in age-related inflammation

The role of the T cell in age-related inflammation

Cellular senescence impact on immune cell fate and function

Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8+T Cells and Cytomegalovirus Replication after Transplantation

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Product

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Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8⁺T Cells and Cytomegalovirus Replication after Transplantation