Hallmark Features of Immunosenescence Are Absent in Familial Longevity

Derhovanessian, Evelyna; Maier, Andrea B.; Beck, Robert; Jahn, Gerhard; Hähnel, Karin; Slagboom, P. Eline; Craen, Anton J. M. de; Westendorp, Rudi G.J.; Pawelec, Graham

doi:10.4049/jimmunol.1001629

Cited by 150 publications

(148 citation statements)

References 33 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…Neither were any of these markers informative within the CD8 subset, probably because the age-associated changes already seen in the controls were so marked that any additional alterations in the patient group were not visible. We know that the age-associated changes seen in CD8+ T cells are predominantly caused by persistent infection with, and hence chronic antigenic stimulation by, CMV, because CMV-negative individuals do not manifest these changes at older age (Chidrawar et al, 2009;Derhovanessian et al, 2010). In contrast, the CD4+ cells are only marginally or much less affected by CMV serostatus (Derhovanessian et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…We know that the age-associated changes seen in CD8+ T cells are predominantly caused by persistent infection with, and hence chronic antigenic stimulation by, CMV, because CMV-negative individuals do not manifest these changes at older age (Chidrawar et al, 2009;Derhovanessian et al, 2010). In contrast, the CD4+ cells are only marginally or much less affected by CMV serostatus (Derhovanessian et al, 2010). Thus, the striking findings of differences within the CD4 subset between AD patients and age-matched controls reported here cannot be caused by CMV; also all elderly controls as well as AD patients were CMV-seropositive.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

Self Cite

132

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

Self Cite

132

View full text Add to dashboard Cite

show abstract

“…We have shown previously that in CMV‐seropositive patients with CHD, the degree of telomere erosion in CD8 cells correlates with deterioration of left ventricular function, linking immunosenescence and cardiovascular disease (Spyridopoulos et al ., 2009; Hoffmann et al ., 2015). In offspring of longevity families, individuals do not show CMV‐associated changes to their immune signatures, suggesting a genetic component in the immune response to CMV (Derhovanessian et al ., 2010). The goal of our study was to evaluate whether in octogenarians CMV seropositivity and T‐cell senescence are independent predictors of all‐cause and especially cardiovascular and CHD‐mediated mortality.…”

Section: Introductionmentioning

confidence: 99%

“…The study by Bartlett took CMV seropositivity into consideration, but not T‐cell immunity specifically (Bartlett et al ., 2012). Derhovassian and coworkers have shown that the response to CMV can be very heterogeneous and that immunological control of the virus can contribute to decreased mortality rate (Derhovanessian et al ., 2010). Our results suggest CMV seropositivity as a driver of T‐cell senescence that at least in the CD4 compartment independently predicts cardiovascular mortality.…”

Section: Introductionmentioning

confidence: 99%

CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study

et al. 2015

View full text Add to dashboard Cite

SummaryAlthough chronic infection with cytomegalovirus (CMV) is known to drive T lymphocytes toward a senescent phenotype, it remains controversial whether and how CMV can cause coronary heart disease (CHD). To explore whether CMV seropositivity or T‐cell populations associated with immunosenescence were informative for adverse cardiovascular outcome in the very old, we prospectively analyzed peripheral blood samples from 751 octogenarians (38% males) from the Newcastle 85+ study for their power to predict survival during a 65‐month follow‐up (47.3% survival rate). CMV‐seropositive participants showed a higher prevalence of CHD (37.7% vs. 26.7%, P = 0.030) compared to CMV‐seronegative participants together with lower CD4/CD8 ratio (1.7 vs. 4.1, P < 0.0001) and higher frequencies of senescence‐like CD4 memory cells (41.1% vs. 4.5%, P < 0.001) and senescence‐like CD8 memory cells (TEMRA, 28.1% vs. 6.7%, P < 0.001). CMV seropositivity was also associated with increased six‐year cardiovascular mortality (HR 1.75 [1.09–2.82], P = 0.021) or death from myocardial infarction and stroke (HR 1.89 [107–3.36], P = 0.029). Gender‐adjusted multivariate Cox regression analysis revealed that low percentages of senescence‐like CD4 T cells (HR 0.48 [0.32–0.72], P < 0.001) and near‐senescent (CD27 negative) CD8 T cells (HR 0.60 [0.41–0.88], P = 0.029) reduced the risk of cardiovascular death. For senescence‐like CD4, but not near‐senescent CD8 T cells, these associations remained robust after additional adjustment for CMV status, comorbidities, and inflammation markers. We conclude that CMV seropositivity is linked to a higher incidence of CHD in octogenarians and that senescence in both the CD4 and CD8 T‐cell compartments is a predictor of overall cardiovascular mortality as well as death from myocardial infarction and stroke.

show abstract

“…CMV encodes several highly immunogenic antigens and a high proportion of the total CD8 + T cell repertoire is specific for CMV in seropositive donors (Kern et al 1999(Kern et al , 2002Lidehall et al 2005;Sylwester et al 2005). CMV infection increases the lymphocyte count and tilts the composition of the T cell compartment towards a lower frequency of naive T cells and accumulation of memory T cells with a late differentiated phenotype (Chidrawar et al 2009;Derhovanessian et al 2010;Pawelec et al 2009). Recently, animal studies have shown that infection with murine CMV induces a massive accumulation of effector memory T cells in aged mice, resulting in impaired T cell mediated antiviral protection, thus strongly supporting a causative role for CMV in immunosenescence (Mekker et al 2012;Cicin-Sain et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

Bengnér

Béziat

Ernerudh

et al. 2013

AGE

View full text Add to dashboard Cite

Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio<1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8+T cells seen in individuals with CD4/CD8 ratio<1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMVseropositive individuals had higher frequencies of CD57+and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.

show abstract

Hallmark Features of Immunosenescence Are Absent in Familial Longevity

Abstract: Material

Cited by 150 publications

References 33 publications

Immune profiling of Alzheimer patients

Immune profiling of Alzheimer patients

CMV seropositivity and T‐cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study

Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

Contact Info

Product

Resources

About