Reversing T cell immunosenescence: why, who, and how

Immunosenescence is the term commonly used to describe the multifaceted phenomenon encompassing all changes occurring in the immune system during aging. It contributes to render older adults more prone to develop infectious disease and main age-related diseases. While age clearly imposes drastic changes in immune physiology, older adults have heterogeneous health and immune phenotypes. This confronts scientists and researcher to develop more age-specific interventions rather than simply adopting intervention regimes used in younger people and this in order to maintain immune protection in older adults. Thus, this review provides evidences of the central role played by cell-mediated immunity in the immunosenescence process and explores the means by which senescent state of the cell-mediated immune function could be identified and predicted using biomarkers. Furthermore considerations are given to recent advances made in the field of age-specific immune interventions that could contribute to maintain immune protection, to improve quality of life, and/or to promote healthy aging of the growing part of the populatio

Can we translate vitamin D immunomodulating effect on innate and adaptive immunity to vaccine response?

Vitamin D (VitD), which is well known for its classic role in the maintenance of bone mineral density, has now become increasingly studied for its extra-skeletal roles. It has an important influence on the body's immune system and modulates both innate and adaptive immunity and regulates the inflammatory cascade. In this review our aim was to describe how VitD might influence immune responsiveness and its potential modulating role in vaccine immunogenicity. In the first instance, we consider the literature that may provide molecular and genetic support to the idea that VitD status may be related to innate and/or adaptive immune response with a particular focus on vaccine immunogenicity and then discuss observational studies and controlled trials of VitD supplementation conducted in humans. Finally, we conclude with some knowledge gaps surrounding VitD and vaccine response, and that it is still premature to recommend "booster" of VitD at vaccination time to enhance vaccine response

An Age-Associated Decline in Thymic Output Differs in Dog Breeds According to Their Longevity

The age associated decline in immune function is preceded in mammals by a reduction in thymic output. Furthermore, there is increasing evidence of a link between immune competence and lifespan. One approach to determining thymic output is to quantify signal joint T cell receptor excision circles (sj-TRECs), a method which has been developed and used in several mammalian species. Life expectancy and the rate of aging vary in dogs depending upon their breed. In this study, we quantified sj-TRECs in blood samples from dogs of selected breeds to determine whether there was a relationship between longevity and thymic output. In Labrador retrievers, a breed with a median expected lifespan of 11 years, there was an age-associated decline in sj-TREC values, with the greatest decline occurring before 5 years of age, but with sj-TREC still detectable in some geriatric animals, over 13 years of age. In large short-lived breeds (Burnese mountain dogs, Great Danes and Dogue de Bordeaux), the decline in sj-TREC values began earlier in life, compared with small long-lived breeds (Jack Russell terriers and Yorkshire terriers), and the presence of animals with undetectable sj-TRECs occurred at a younger age in the short-lived breeds. The study findings suggest that age-associated changes in canine sj-TRECs are related to breed differences in longevity, and this research highlights the use of dogs as a potential model of immunosenescence

Ageing and the immune system in vivo: commentary on the 16th session of British Society for Immunology Annual Congress, Harrogate, December 2004

The problems associated with the ageing immune system coupled with possible solutions were discussed recently at the British Society for Immunology Annual Congress in Harrogate in December 2004. The session "Ageing and the Immune System in vivo" dealt in details with the immune risk phenotype and the potential methods of reversing the problems of an ageing immune system. This is a commentary on that session

Gender-Related Differences in the Rates of Age Associated Thymic Atrophy

Age associated thymic atrophy has been shown to be linked to problems with rearrangement of the β chain of the T cell receptor (TCR) in male mice during the early phases of the intrathymic T cell developmental pathway. In this study, thymic atrophy in female mice was found to occur at a different rate than in male mice. At 9 months of age there was a significantly greater number of cells in the thymus of female mice compared with male mice, with the major difference found in the CD4+CD8+ populations. The thymii of female mice at 9 months of age contained double the number of these cells compared with male mice. Analysis of the CD4+CD8+ cells at 9 months of age demonstrated increased numbers of cells expressing higher levels of CD3 in females compared with males indicating that in females more of these cells were producing successful αβTCR pairings. In F5 transgenic mice comparison of the CD4+CD8+ population revealed no significant difference in their absolute numbers at 9 months of age. These results indicate that the gender differences at this time point were due to fewer permitted divisions prior to the expression of a selectable TCR α chain within the CD4+CD8+ populations in male compared with female mice. This gender difference was not due to the action of testosterone and unlikely to be due to differences in the level of oestrogen. The potential mechanisms of this difference may be related to a regulatory feedback of peripheral T cells on the developing thymocyte populations. Such age related changes in the numbers of cells within distinct thymic subpopulations leads to the possibility that the potential repertoire in females is greater than in males later in life

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Emergent Properties of Land Systems: Nonlinear Dynamics of Scottish Farming Systems from 1867 to 2020

Dynamics of arable and pastoral farming systems in Scotland over the period 1867-2020 are documented using time series analysis methods, including for nonlinear dynamical systems. Results show arable and pastoral farming, at a national scale, are dynamic over a range of timescales, with medium- and short-term dynamics associated with endogenous system forces and exogenous factors, respectively. Medium-term dynamics provide evidence of endogenous systems-level feedbacks between farming sectors responding to change in world and national cereal prices as an economic driver, and act to dampen impacts of exogenous shocks and events (weather, disease). Regime shifts are identified in national cereal prices. Results show change and dynamics as emergent properties of system interactions. Changes in dynamics and strength of endogenous dampening over the duration of the study are associated with dynamical changes from major governmental policy decisions that altered the boundary conditions for interdependencies of arable and pastoral farming

A qualitative analysis of the effectiveness of telehealthcare devices (i) are they meeting the needs of end-users?

Background: There are many telehealthcare devices currently available ranging from personal alarms, automated pill dispensers and fall detectors through to monitoring devices for blood sugar, blood pressure and heart rate. Many devices remain unused once acquired or shortly after a period of initial use. Methods: The study used a qualitative design involving focus groups and interviews. End users’ opinions of telehealthcare devices were examined through focus groups along with the views of market experts and key supply chain players through telephone interviews to ascertain their views on the devices. The data were recorded, transcribed and analysed thematically. Results: Amongst the wide range of user issues associated with telehealthcare devices two themes merited particular attention: design characteristics and the lack of focus on end-user needs. Our findings suggested that few telehealthcare devices appear to be developed based on the principles of user-centred design. Consequently, many were non-intuitive to use, with the majority of the focus group participants not recognising the purpose of the devices from their appearance alone. Conclusions: Greater input from real end-users rather than “proxy” users such as carers, professional users or technologists is required when developing telehealthcare devices or systems. Design should be focussed on intuitive use to enable the user to successfully achieve what is required from the devices. This may require the existing supplier—driven market focus to be challenged, but could improve the contribution of technology to improving healthcare