Aging disturbs the balance between effector and regulatory CD4+ T cells

Geest, Kornelis S M van der; Abdulahad, Wayel H.; Tete, Sarah M.; Lorencetti, Pedro G.; Horst, G.; Bos, Nicolaas A.; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M. H.

doi:10.1016/j.exger.2014.11.005

Cited by 104 publications

(81 citation statements)

References 33 publications

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“…Consistent with previous studies (Hwang et al 2009), in the present study most of the CD4 + CD25 ++ CD127 −/low cells had the memory phenotype (CD45RA -). Unlike other studies (Miyara et al 2009;Booth et al 2010;van der Geest et al 2014) that showed that the proportions of circulating naïve Tregs decreased with age, whereas memory Treg cells were increased (a tendency observed for our control group), we observed a tendency to maintain / increase the proportions of the naïve cells in the Masters athlete group, while a maintenance / reduction was observed in the control group (Figure 4). This however was not statistically significant and a higher number of subjects will need to be analysed to substantiate, or not, these findings.…”

Section: Discussioncontrasting

confidence: 99%

“…Although both naïve and memory Tregs are suppressive, they possess distinct homing receptors that allow migration into either lymphoid organs or inflamed tissues, respectively (Miyara et al 2009;van der Geest et al 2014). Naïve Tregs might play an important role in the maintenance of the Treg pool in adults, whereas the increase of memory Treg cells was associated with a decreased humoral response to vaccine (van der Geest et al 2014). Based on the expression of CD45RA, we divided CD4 + T cells into naïve (CD45RA + ) and memory (CD45RA -) cells, but no differences in naïve and memory populations were found between controls and Masters.…”

Section: Discussionmentioning

confidence: 99%

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Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes

et al. 2017

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2 AbstractPurpose: The purpose of this study was to quantify and characterize peripheral blood regulatory T cells (Tregs), as well as the IL-10 plasma concentration, in Masters athletes at rest and after an acute exhaustive exercise test. Methods: Eighteen Masters athletes (self-reported training: 24.6±1.83 years; 10.27±0.24 months and 5.45±0.42 hours/week per each month trained) and an age-matched control group of 10 subjects (that never took part in regular physical training) volunteered for this study. All subjects performed an incremental test to exhaustion on a cycle ergometer. Blood samples were obtained before (Pre), 10min into recovery (Post) and 1h after the test (1h). Results: Absolute numbers of Tregs were similar in both groups at rest. Acute exercise induced a significant increase in absolute numbers of Tregs at Post (0.0490.021 to 0.0560.024 x10 9 /L, P=0.029 for Masters; 0.0480.017 to 0.0580.020 x10 9 /L, P=0.037 for control) in both groups. Treg mRNA expression for Foxp3, IL-10 and TGF-β in sorted Tregs was similar throughout the trials in both groups. Masters athletes showed a higher percentage of subjects expressing the FoxP3 (100% for Masters vs. 78% for Controls, P=0.038) and TGF- (89% for Masters vs. 56% for Controls, P=0.002) after exercise and a higher plasma IL-10 concentration (15.3907.032 for Masters vs. 2.4111.117 for control P=0.001, ES =2.57) at all time-points. KLRG1 expression in Tregs was unchanged. Conclusion: Our findings showed that Masters athletes have elevated anti-inflammatory markers and maintain the number of Tregs, may be an adaptive response to lifelong training.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes

et al. 2017

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“…Anti-TNF therapy did not seem to increase the risk of lymphoma (any), solid tumors or NMSC in both primary and secondary analysis in young or the elderly (≥ 65), although the mean follow-up time was only 1 year. Again, in the secondary analysis of the 15 etanercept trials (LRA, ERA and TEMPO) the cancer rate in the older RA patients did not differ between the etanercept and control groups [56,46,61]. NSAIDs, glucocorticoid use and a history of solid or haematologic cancer are independent risk factors [35].…”

Section: 12tolerability and Safetymentioning

confidence: 90%

“…The proportion of naïve regulatory T cells decreases with age, but their absolute numbers stay relatively stable as the proportion and the absolute numbers of memory T cells increase. Additionally, the total CD4+T cell counts significantly increase with age and CD8+T cell counts decrease, resulting in significantly raised CD4/CD8 ratio in elderly subjects [15]. Furthermore, both T cells subsets undergo changes in their receptor expression and thereby in their function.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

Ishchenko

Lories

2016

Drugs Aging

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The population of elderly individuals with rheumatoid arthritis is rapidly expanding, mainly due to the increased life expectancy. While targeted biological therapies are well established for the treatment of this disease, their use may be lower in elderly (> of 65 years old) and very elderly patients (> 75 years old) due to perceived higher risks for adverse events in this population taking into account comorbidity, polypharmacy and frailty. In this review we discuss available evidence for the use of biological therapies in this growing patient group with specific attention towards eventual reasons for biological treatment failure or withdrawal. The majority of data is found in secondary analyses of clinical trials and in retrospective cohorts. Most information is available about tumor necrosis factor (TNF) blockers. Older patients seem to have a less robust response to anti-TNF agents than a younger population, but drug survival that may considered a proxy for efficacy does not seem to be influenced by age. Despite an overall rate of adverse effects comparable to that in younger patients, elderly RA patients are at higher risk of serious infections. Other biologics appear to have an efficacy similar to anti-TNF agents, also in the elderly RA patients. Again, the drug survival rates for tocilizumab, rituximab and abatacept resemble those in young RA patients with good general tolerability and safety profiles. The cardiovascular risk and the risk of cancer, increased in RA patents and in the elderly patients, do not appear to be strongly influenced by biologicals. Key points-Biological drugs targeting specific cytokines or immune cell populations are an important part of the management strategy for rheumatoid arthritis patients, including the elderly. 3-Overall safety and tolerability in the elderly patients is very good and age should not be a critical factor to decide against biological drug use.-The drug survival rate of biologicals in the elderly RA patients is comparable to that in the young RA population.-Co-morbidities and risk of infection are important variables to assess when considering a biological drug in the elderly.-More data and specific studies are required to better position biological drug use in this particular population as current studies provide a low level of evidence. Data in patients above 75 years are still largely missing. Moreover, the group of elderly patients that were included in clinical trials may be influenced by selection bias at inclusion and not be fully representative for infections risks and other comorbidities.4

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“…The effects of aging on the immune system are widespread. It is proposed that the ratio of naive T-cells to memory T-cells declines, an increase in the number of memory T-cells is now a particularly well-recognized feature of aging (10,(28)(29)(30)(31). Based on the current study findings, an increase of memory CD4 + T-cells was observed in the patients with type 2 DM and controls with aging; while, naive CD4 + T-cells appeared not to be associated with age in both groups.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes Mellitus Associated with Premature Aging

Bilici

Arpacı

İlikhan

et al. 2017

Iran Red Crescent Med J

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Background: A decrease of naive T-cells and a concomitant increase in memory cells are the accepted consequences of aging on the adaptive immune system. Objectives: The current case-control study aimed at considering the impact of chronic hyperglycemia that leads to glycation of modified self proteins on aging via the memory cell percentages among the patients admitted to the endocrinology department of Bulent Ecevit University Hospital in Zonguldak province, Turkey, from September to October 2015. Methods: Blood samples were collected from 81 patients with diabetes mellitus (DM) and 39 healthy volunteers with no history of autoimmune diseases or chronic inflammatory disorders, based on the purposive sampling method. The patients were divided into 2 groups based on the presence and absence of the diabetic microvascular complications. Diabetic nephropathy, neuropathy, and retinopathy were investigated according to the American Diabetes Association criteria. T-lymphocytes subpopulations were measured in peripheral blood by the flow cytometry. CD27, CD45 RO, and CD45 RA were used to discriminate naive and memory T-cells (CD4 + and CD8 + ). Data for each subpopulation were reported as a percentage of the total CD4 + and CD8 + cells.

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Aging disturbs the balance between effector and regulatory CD4+ T cells

Cited by 104 publications

References 33 publications

Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes

Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

Type 2 Diabetes Mellitus Associated with Premature Aging

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