CD8 T-cell immune phenotype of successful aging

Hsu, Hui Chen; Scott, Donald K.; Zhang, Pili; Zhou, Juling; Yang, Ping; Wu, Qi; Schroeder, Harry W.; Gerald, Lynn B.; Ravussin, Éric; Jazwinski, S. Michal; Mountz, John D.; Batzer, Mark A.; Black, M; Broussard, E. A.; Byerley, Laurie; Callinan, Pauline; Cherry, Katie E.; Chiu, Yu Wen; Cooper, Annie; DeLany, James P.; Deutsch, Walter; Fontham, Elizabeth T.H.; Frisard, Madlyn I.; Geiselman, Paula J.; Greco, Valentina; Hawley, Karri S.; Herke, Scott W.; Kendzor, Darla E.; Kim, Sang-Kyu; Kimball, Beth C.; Li, Li; Lopez, Kay; Robertson, Yolanda; Rothschild, Henry; Schmidt, Beth; Standberry, F. Nicole; Su, Li; Lin, Hui Yi; Traylor, Crystal P.; Wood, Robert H.

doi:10.1016/j.mad.2005.10.001

Cited by 20 publications

(22 citation statements)

References 36 publications

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“…Proliferation of PBMCs after PHA stimulation was determined using the [ 3 H]-thymidine incorporation method, as we previously described [33, 34]. Briefly, the PBMC cultures were pulsed with [3H]-thymidine (Amersham Pharmacia Biotech) 18 h before harvest.…”

Section: Methodsmentioning

confidence: 99%

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging

Hwang¹,

Hsu²,

Lim³

et al. 2013

AAR

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Given the protective roles of 25-hydroxyvitamin D (25[OH]D or vitamin D) in musculoskeletal health and the potential beneficial effects of vitamin D supplementation in reducing the risk of various chronic diseases, intensive repletion of vitamin D has been widely advocated. Of note, CD8 T cells have the highest levels of the vitamin D receptor compared with other major immune cells. The effects of vitamin D on CD8 T cells during aging, however, remain unclear. This study determined the relationship between vitamin D levels and CD8 T-cell status in 34 healthy female subjects (all >60 years old). The CD8 T cell phenotype was defined by the surface expression of CD28 and CD95. The low-25(OH)D serum groups (≤30 ng/ml) had higher percentages of CD28+CD95−CD8+ (naïve) T cells and lower percentages of CD28+CD95+CD8+ (effector) T cells. By contrast, subjects with high levels of 25(OH)D had very low percentages of naïve CD8 T cells but very high percentages of effector CD8 T cells. There was a significant inverse correlation between 25(OH)D levels and the frequency of naïve CD8 T cells. The results show that higher levels of vitamin D are correlated with decreased frequencies of naïve CD8 T cells during early aging, suggesting that higher levels of 25(OH)D accelerate CD8 T-cell senescence. These results warrant the further evaluation of the effects of vitamin D supplementation in immune aging.

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Section: Methodsmentioning

confidence: 99%

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging

Hwang¹,

Hsu²,

Lim³

et al. 2013

AAR

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“…Among tricuspid CAS cases the percentage of CD8 + CD28 null T cells correlated with valve calcification severity ( = 0.666, p = 0.003). In the much younger bicuspid CAS patients, mean age 56± 18 years, the proportion of CD8 + CD28 null T cells was more than double the level expected in normal agematched individuals (Hsu et al 2006). For all valve types, a greater proportion of CD8 + CD28 null T cells was seen in cases where the valve calcification severity score was ≥ 4 (p = 0.0006), and the correlation with calcification score was  = 0.590, p = 0.001.…”

Section: Wwwintechopencommentioning

confidence: 72%

“…The alteration in T cell phenotype during an immune response, especially evident in the CD8 T cells, usually includes the transient expression of activation molecules, such as HLA-DR (Yu et al 1980) and/or CD69, and the development of memory-effector cells particularly in sustained responses, defined by the loss of co-stimulatory CD28 molecules and acquisition of structures including natural killer receptors, e.g. CD57 (Brenchley et al 2003, Hsu et al 2006, Sallusto et al 2004, Speiser et al 1999. The presence of these features was studied by using flow cytometry to determine the expression of activation markers on the peripheral blood T cells and their subsets .…”

Section: The Inflammatory Infiltrate In Bicuspid and Tricuspid Valve mentioning

confidence: 99%

The Inflammatory Infiltrate in Calcific Aortic Stenosis is Characterized by Clonal Expansions of T Cells and is Associated with Elevated Proportions of Circulating Activated and Effector Memory CD8 T Cells

Winchester¹,

Kodali²

2011

Aortic Stenosis - Etiology, Pathophysiology and Treatment

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“…Immune cells that undergo programmed cell death include various lymphocyte populations, macrophages, dendritic cells and neutrophils (4,(19)(20)(21). Apoptotic loss of immune effector cells such as CD4 T and B cells is a key factor in the loss of immune competence in sepsis (22,23).…”

Section: Discussionmentioning

confidence: 99%

Accelerated apoptosis contributes to aging-related hyperinflammation in endotoxemia

Zhou

Wu²,

Dong³

et al. 2010

Int J Mol Med

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Abstract. Sepsis is associated with an increase in circulating levels of bacterial endotoxin. Sepsis is a particularly serious problem in the geriatric population due to the associated high mortality rate. However, it remains unknown whether this phenomenon is related to an increase in apoptosis in splenic cells. To investigate this issue, male Fischer-344 rats (young, 3 months old; aged, 24 months old) were subjected to endotoxemia by injection of LPS. Splenic samples were collected 4 h thereafter. Apoptosis was determined by cleaved caspase-3 levels and TUNEL staining. The levels of proinflammatory mediators, TNF-·, IL-6 and high mobility group box-1 (HMGB-1), were also measured. Our results showed that, while splenic cell apoptosis increased in the young and aged rats with endotoxemia, the aged animals had much higher levels of apoptotic cell death. The elevated expression of cell cycle inhibitory protein P21 was also observed in the aged animals after treatment with LPS. Moreover, endotoxemia significantly increased TNF-·, IL-6 and HMGB-1. The accelerated apoptosis in the aged animals was correlated with significantly higher levels of TNF-·, IL-6 and HMGB-1. It is suggested that this accelerated rate of apoptosis contributes to age-related hyperinflammation in endotoxemia. To investigate the factors involving accelerated apoptosis in aged animals, we analyzed the Fas/Fas ligand (Fas-L) pathway. Our results showed that Fas and Fas-L gene expression was markedly higher in the spleen in the aged animals after LPS. Similarly, cleaved caspase-8 expression, a downstream element of Fas and Fas-L, was also significantly higher in the aged rats after LPS. Fas-L neutralizing antibodies markedly decreased apoptosis and proinflammatory cytokines in the aged animals after endotoxemia. Thus, there is substantial evidence that the Fas/Fas-L pathway may play an important role in LPS-induced accelerated apoptosis and hyperinflammation in aged animals.

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CD8 T-cell immune phenotype of successful aging

Cited by 20 publications

References 36 publications

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging

The Inflammatory Infiltrate in Calcific Aortic Stenosis is Characterized by Clonal Expansions of T Cells and is Associated with Elevated Proportions of Circulating Activated and Effector Memory CD8 T Cells

Accelerated apoptosis contributes to aging-related hyperinflammation in endotoxemia

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CD8 T-cell immune phenotype of successful aging

Cited by 20 publications

References 36 publications

Increased vitamin D is associated with decline of na&#239;ve, but accumulation of effector, CD8 T cells during early aging

Increased vitamin D is associated with decline of na&#239;ve, but accumulation of effector, CD8 T cells during early aging

The Inflammatory Infiltrate in Calcific Aortic Stenosis is Characterized by Clonal Expansions of T Cells and is Associated with Elevated Proportions of Circulating Activated and Effector Memory CD8 T Cells

Accelerated apoptosis contributes to aging-related hyperinflammation in endotoxemia

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Product

Resources

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Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging