2,828 research outputs found
Physical Exercise and its Implications for Aging Immunity and Adoptive Transfer Immunotherapy
Advancing age is associated with a profound decline in the normal functioning of the immune system that is commonly referred to as immunosenescence. Impaired responses to vaccination and the increased incidence of infection and malignancy seen in the elderly are often considered to be a direct consequence of immunosenescence. A large body of cross-sectional data has shown that habitual exercise is associated with enhanced functional responses in both the innate and adaptive arms of the aging immune system, indicating that exercise may help curtail the onset of immunosenescence. However, it is not known if exercise is also capable of reversing the detrimental effects of aging on an already weakened immune system. The first part of this presentation will focus on the known effects of habitual exercise at preserving the aging immune system and discuss avenues for future research to test the hypothesis that exercise has immune rejuvenating properties in the elderly.
Cancer is widely considered to be an age-related disease, with hematopoietic stem cell transplantation (HSCT) being the preferred treatment for many patients with hematologic malignancies. However, HSCT is associated with significant morbidity and mortality especially due to viral infections (i.e. cytomegalovirus, Epstein-Barr virus and adenovirus) and relapse. The second part of this presentation will focus on the immuno-enhancing effects of acute exercise as a means of increasing the efficacy of adoptive transfer immunotherapy - the passive infusion of ex vivo expanded donor-derived or autologous immune cells to a cancer patient recipient. Our early work in this area indicates that a single bout of exercise can augment the ex-vivo expansion of donor-derived NK-cells and antigen-specific T-cells for use in allogeneic adoptive transfer immunotherapy. This may offer a safe and cost-effective method to improve prognosis and reduce mortality in cancer patients after HSCT
The Impact of Latent Herpesvirus Infections on the Mobilization of Recent Thymic Emigrants and Extrathymic T-cells in Response to Acute Aerobic Exercise in Man
T-cells typically mature in the thymus gland, which eventually succumbs to age-related atrophy, resulting in a decreased naïve T-cell repertoire in middle to later years. Aged individuals and those with persistently reactivating herpesvirus infections have an increased reliance on the extrathymic maturation of T-cells due to the shrinking effects that age and latent viral infection has on the naïve T-cell repertoire. Acute bouts of aerobic exercise are known to mobilize T-cells that exhibit both a naïve and late-stage differentiation phenotype into the blood compartment; however, it is not known if recent thymic emigrants (RTE) or extrathymic T-cells contribute to the lymphocytosis associated with exercise. PURPOSE: To examine the impact of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection on the mobilization of RTE and extrathymic T-cells in response to acute exercise. METHODS: Otherwise healthy CMV or EBV seropositive (CMV+ or EBV+) and CMV or EBV seronegative (CMV- or EBV-) males (age 23-35y) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and one hour after exercise were surface stained with monoclonal antibodies to identify phenotypes of RTE (CD103+/CD62L-) and extrathymic T-cells believed to mature in the liver (CD3+/CD25-/CD122+) and the epithelium of the small intestine (CD3+/CD4-/CD8-; TCRγδ+/ CD8αα+; CD3-/CD2+/CD7+). Cell populations were analyzed by flow cytometry and antibodies against CMV and EBV were determined in serum by ELISA. RESULTS: Preliminary analyses show that the proportion of RTE among the total CD3+/CD4+ or CD3+/CD8+ T-cell subsets did not change immediately after exercise, but was elevated above baseline 1h later due to the preferential egress of late stage differentiated T-cells. Neither CMV nor EBV status influenced the proportions of RTE in blood in response to exercise. T-cells mainly found in intestinal mucosa (i.e. CD3+/CD4-/CD8- and CD3-/CD2+/CD7+) were found to increase in blood immediately after exercise; an effect that appeared to be more pronounced in EBV but not CMV-infected subjects. CONCLUSION: An acute bout of aerobic exercise elicits the mobilization of T-cells exhibiting phenotype characteristics of extrathymically matured T-cells, suggesting that extrathymic T-cell mobilization contributes to the lymphocytosis associated with acute exercise. This effect appears to be amplified in subjects carrying a latent EBV but not CMV infection. Future research should attempt to establish the impact of long-term exercise and latent herpesvirus infections on the frequency of RTE and extrathymic T-cells in the aged, as this could have significant implications for age-associated immune dysfunction
A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy
Investigating the Cusp between the Nano- and Macro-sciences in Supermolecular Liquid-Crystalline Twist-Bend Nematogens
In this article we report the first known linear liquid-crystalline hexamer and in doing so demonstrate that higher oligomers and main chain polymers, with chemical structures based upon dimers and bimesogens, can exhibit the topical twist-bend ‘nematic’ mesophase. In doing so we find that there is continuation of properties and structures across the spectrum from dimer to polymer and possibly to macroscale objects such as helical flagella. This finding highlights the cross over from nanoscience based mainly on electrostatics and other non-covalent interactions to macroscience based mainly on molecular topology, density of packing, and minimisation of the free energy
The impact of latent CMV infection on NK-cell mobilization and expression of KLRG1 and CD57 in response to acute exercise.
Natural killer (NK) cells are cytotoxic effectors of the innate immune system that are able to distinguish healthy autologous cells from tumors and virally infected cells. NK-cells kill the targeted cells by releasing cytotoxic proteins, a process that is governed by inhibitory surface receptors, such as KLRG1. Additionally, activated NK-cells are able to proliferate in response to immunological stimuli, a process that is inhibited in NK-cells expressing the senescence marker CD57. Acute bouts of exercise are known to mobilize NK cells into the blood compartment, which could alter immunity; however, whether or not exercise alters NK-cell KLRG1 and CD57 expression has not been fully elucidated. Furthermore, as latent CMV infection is associated with an increased frequency of inhibitory NK cells, it is not known if CMV status influences NK-cell mobilization in response to acute exercise. PURPOSE: To examine the impact of latent CMV infection on the mobilization of NK-cells and their expression of KLRG1 and CD57 in response to acute exercise. METHODS: Otherwise healthy CMV seropositive (CMV+) and CMV seronegative (CMV-) males (age 23-35 years) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and one hour after exercise were surface-stained with monoclonal antibodies against CD3, CD56, KLRG1 and CD57 and analyzed by 4-color flow cytometry. RESULTS: Preliminary analysis of the data show a prodigious increase in the number of CD56 dim (mature, highly cytotoxic subset) NK-cells immediately after exercise in all subjects, which subsequently fell below pre-exercise values 1 hour later. In CMV- subjects, the proportion of CD56 bright (immature, mildly cytotoxic) NK cells was considerably higher 1 hour post-exercise than before exercise, but the number of cells changed very little suggesting that the increased proportion was due merely to the egress of CD56 dim NK cells. Interestingly, CMV seropositivity was associated with a near complete absence of CD56 bright NK cells that was unaffected by exercise. Neither exercise nor CMV status influenced the proportion of NK-cells expressing KLRG1 or CD57. CONCLUSION: Preliminary analysis of this data indicates that acute exercise preferentially mobilizes CD56 dim NK cells without altering KLRG1 and CD57 expression. Latent CMV infection is associated with a lowered proportion of CD56 bright NK-cells; however, the NK-cell response to exercise was not influenced by CMV status. Future work will examine the role of aging on NK-cell response to exercise and CMV status
Regional disparities and seasonal differences in climate risk to rice labour.
The 880 million agricultural workers of the world are especially vulnerable to increasing heat stress due to climate change, affecting the health of individuals and reducing labour productivity. In this study, we focus on rice harvests across Asia and estimate the future impact on labour productivity by considering changes in climate at the time of the annual harvest. During these specific times of the year, heat stress is often high compared to the rest of the year. Examining climate simulations of the Coupled Model Intercomparison Project 6 (CMIP6), we identified that labour productivity metrics for the rice harvest, based on local wet-bulb globe temperature, are strongly correlated with global mean near-surface air temperature in the long term (p ≪ 0.01, R 2 > 0.98 in all models). Limiting global warming to 1.5 °C rather than 2.0 °C prevents a clear reduction in labour capacity of 1% across all Asia and 2% across Southeast Asia, affecting the livelihoods of around 100 million people. Due to differences in mechanization between and within countries, we find that rice labour is especially vulnerable in Indonesia, the Philippines, Bangladesh, and the Indian states of West Bengal and Kerala. Our results highlight the regional disparities and importance in considering seasonal differences in the estimation of the effect of climate change on labour productivity and occupational heat-stress
Efficient Use of Phosphorus in Temperate Grassland Systems
Phosphorus (P) fertilisers are important for high production in many grassland systems. However, there are increasing environmental, economic and strategic issues associated with using P, which is a non-renewable and “effectively finite” global resource. We review the P balance of temperate pastures to identify the factors that contribute to inefficient P use and discuss ways to improve P use efficiency. The most immediate gains can be made by ensuring that pastures are not over-fertilised. Plants with low critical P requirements, particularly as a result of better root foraging, will be important. Root traits such as fine roots (root diameter), branching, length and root hairs, and mycorrhizal associations all contribute to improved root foraging; some are amenable to plant breeding. Plants that can “mine” sparingly-available P in soils by producing organic anions and phosphatases are also needed; as are innovations in fertiliser technology. Soil microorganisms play a crucial role in P acquisition by pastures but are not particularly amenable to management. Selection of pasture species for root characteristics offers a more realistic approach to improving P efficiency but progress, to date, has been minimal. Traditional plant breeding, augmented by marker assisted selection and interspecific hybridisation, are likely to be necessary for progress. Inevitably, P efficient pastures will be achieved most effectively by a combination of plant genetic, fertiliser innovation and management responses. Success will bring economic and environmental benefits from reduced P fertiliser use, with consequent benefits for global resource and food security
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