T-cell-derived TNF-α and a cluster of immunological parameters from plasma allow a separation between SARS-CoV-2 convalescent versus vaccinated elite athletes.

Guidelines for medical clearing after SARS-CoV-2 infection in elite athletes do not include T-cell immunity aspects despite its relevance in the course of COVID-19 disease. Therefore, we aimed to analyze T-cell-related cytokines before and after in-vitro activation of CD4+ T-cells. We sampled professional indoor sports athletes at medical clearing after SARS-CoV-2 infection obtaining clinical, fitness data, and serological data including CD4+ T-cell cytokines. All data were analyzed by principal component analysis and 2 × 2 repeated measures ANOVA. CD4+ T-cells were sampled for cell culture activation with anti-CD3/anti-CD28 tetramers. At medical clearing, CD4+ T-cells from convalescent athletes secreted increased levels of TNF-α 72 h after in-vitro activation compared to vaccinated athletes. IL-18 levels in plasma were elevated and a cluster of parameters differentiated convalescent from vaccinated athletes by 13 parameters at the timepoint of medical clearing. All clinical data indicate infection is resolved, while increased TNF-α may reflect altered proportions of peripheral T-cells as a hangover of infection.

12-week combined strength and endurance exercise attenuates CD8+ T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial.

BACKGROUND: Age-related accumulation of highly differentiated CD8+ effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+ T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50-70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+ T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined. RESULTS: The CD8+ EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05). CONCLUSIONS: Combined strength and endurance training seems to be a suitable approach to attenuate CD8+ T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.

Neurophysiological Markers for Monitoring Exercise and Recovery Cycles in Endurance Sports.

The current study analyzes the suitability and reliability of selected neurophysiological and vegetative nervous system markers as biomarkers for exercise and recovery in endurance sport. Sixty-two healthy men and women, endurance trained and moderately trained, performed two identical acute endurance tests (running trial 1 and running trial 2) followed by a washout period of four weeks. Exercise protocol consisted of an acute running trial lasting 60 minutes. An intensity corresponding to 95% of the heart rate at individual anaerobic threshold for 40 minutes was followed by 20 minutes at 110%. At pre-exercise, post-exercise, three hours post-exercise and 24 hours post-exercise, experimental diagnostics on Brain-derived neurotrophic factor (BDNF), heart rate variability (HRV), Stroop Color and Word Test (SCWT), and Short-Form McGill Pain Questionnaire (SF-MPQ) were performed. Significant changes over time were found for all parameters (p < .05). Furthermore, there was an approached statistical significance in the interaction between gender and training status in BDNF regulation (F(3) = 2.43; p = 0.06), while gender differences were found only for LF/HF-ratio (3hPoEx, F(3) = 3.40; p = 0.002). Regarding the reliability, poor ICC-values (< 0.5) were found for BDNF, Stroop sensitivity and pNN50, while all other parameters showed moderate ICC-values (0.5-0.75). Plasma-BDNF, SCWT performance, pain perception and all HRV parameters are suitable exercise-sensitive markers after an acute endurance exercise. Moreover, pain perception, SCWT reaction time and all HRV parameters show a moderate reliability, others rather poor. In summary, a selected neurophysiological and vegetative marker panel can be used to determine exercise load and recovery in endurance sports, but its repeatability is limited due to its vaguely reliability.

Immunometabolism-fit: How exercise and training can modify T cell and macrophage metabolism in health and disease.

BACKGROUND: The term immunometabolism describes cellular and molecular metabolic processes that control the immune system and the associated immune responses. Acute exercise and regular physical activity have a substantial influence on the metabolism and the immune system, so that both processes are closely associated and influence each other bidirectionally. SCOPE OF REVIEW: We limit the review here to focus on metabolic phenotypes and metabolic plasticity of T cells and macrophages to describe the complex role of acute exercise stress and regular physical activity on these cell types. The metabolic and immunological consequences of the social problem of inactivity and how, conversely, an active lifestyle can break this vicious circle, are then described. Finally, these aspects are evaluated against the background of an aging society. MAJOR CONCLUSIONS: T cells and macrophages show high sensitivity to changes in their metabolic environment, which indirectly or directly affects their central functions. Physical activity and sedentary behaviour have an important influence on metabolic status, thereby modifying immune cell phenotypes and influencing immunological plasticity. A detailed understanding of the interactions between acute and chronic physical activity, sedentary behaviour, and the metabolic status of immune cells, can help to target the dysregulated immune system of people who live in a much too inactive society.

The effect of exercise on regulatory T cells: A systematic review of human and animal studies with future perspectives and methodological recommendations.

Many of the exercise-related health-promoting effects are attributed to beneficial immunomodulation. The restoration of immune homeostasis is context-dependent, meaning either to increase anti-inflammatory signaling to counteract disease progression of non-communicable (auto)inflammatory diseases or to enhance (local) activity of proinflammatory immune cells to slow down or inhibit cancer progression. Regulatory CD4+ T cells (Tregs) represent the main regulatory component of the adaptive immune system that fine-tunes inflammatory responses, keeps them in check and prevents long-lasting autoimmunity. Because often dysregulated in the context of various diseases, emerging treatment approaches aim to modulate their number or inherent anti-inflammatory and immunosuppressive function in a highly disease-specific way. Exercise represents a non-pharmacologic strategy in disease prevention and rehabilitation and may be an effective treatment with few to no side effects to counteract dysregulation of Tregs. To date, several studies have evaluated the effect of exercise on Treg-related outcomes. This review aims at providing a comprehensive overview on alterations of blood- or tissue-derived Treg counts, proportion and functionality following acute and chronic exercise in humans and animal models. From the 60 reviewed studies, an overall disease-specific beneficial effect of chronic exercise on Treg levels in animal models can be stated, while both acute and chronic effects in human studies are less definite. However, Treg phenotyping is less sufficient in the animal studies compared to human studies. Only a limited number of studies investigated Treg functionality. There is a large heterogeneity concerning study design, human population or animal model, exercise protocol, and Treg outcome measure specification which makes it difficult to compare results and draw clear conclusions. Study results are discussed in the context of current concepts in exercise immunology. Finally, future perspectives and methodological recommendations are provided to promote research in this field.

Abdominal Obesity-Related Disturbance of Insulin Sensitivity Is Associated with CD8+ EMRA Cells in the Elderly.

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross-sectional study, we aimed to investigate the potential mediating role of T-EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA-IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower-weight subgroups. Linear regression analysis revealed that an elevated HOMA-IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist-to-hip ratio on HOMA-IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes.

Reasons for and Consequences of Low Energy Availability in Female and Male Athletes: Social Environment, Adaptations, and Prevention.

Low energy availability (LEA) represents a state in which the body does not have enough energy left to support all physiological functions needed to maintain optimal health. When compared to the normal population, athletes are particularly at risk to experience LEA and the reasons for this are manifold. LEA may result from altered dietary behaviours that are caused by body dissatisfaction, the belief that a lower body weight will result in greater performance, or social pressure to look a certain way. Pressure can also be experienced from the coach, teammates, and in this day and age through social media platforms. While LEA has been extensively described in females and female athletes have started fighting against the pressure to be thin using their social media platforms, evidence shows that male athletes are at risk as well. Besides those obvious reasons for LEA, athletes engaging in sports with high energy expenditure (e.g. rowing or cycling) can unintentionally experience LEA; particularly, when the athletes' caloric intake is not matched with exercise intensity. Whether unintentional or not, LEA may have detrimental consequences on health and performance, because both short-term and long-term LEA induces a variety of maladaptations such as endocrine alterations, suppression of the reproductive axis, mental disorders, thyroid suppression, and altered metabolic responses. Therefore, the aim of this review is to increase the understanding of LEA, including the role of an athlete's social environment and the performance effects related to LEA.

Reliability and suitability of physiological exercise response and recovery markers.

There is currently insufficient evidence about the reliable quantification of exercise load and athlete's recovery management for monitoring training processes. Therefore, this test-retest study investigated the reliability of various subjective, muscle force, and blood-based parameters in order to evaluate their suitability for monitoring exercise and recovery cycles. 62 subjects completed two identical 60-min continuous endurance exercise bouts intermitted by a four-week recovery period. Before, immediately after, three, and 24 h after each exercise bout, analysis of parameters were performed. Significant changes over time were found for rating of perceived exertion (RPE), multidimensional mood state questionnaire (MDMQ), maximum voluntary contraction parameters (MVCs), and blood-based biomarkers (p < 0.05). Excellent reliability was calculated for MVCs, mean corpuscular volume and 5-bound distance (ICC > 0.90). A good reliability was found for thiobarbituric acid reactive substances (TBARS) (ICC = 0.79) and haematological markers (ICC = 0.75-0.86). For RPE, MDMQ, interleukin (IL-) 1RA, IL-6, IL-8, IL-15, cortisol, lactate dehydrogenase (LDH), creatine kinase (CK) only moderate reliability was found (ICC < 0.75). Significant associations for IL1-RA and CK to MVC were found. The excellent to moderate reliability of TBARS, LDH, IL-1RA, six measured haematological markers, MVCs and MDMQ implicate their suitability as physiological exercise response and recovery markers for monitoring athletes' load management.

The effect of acute running and cycling exercise on T cell apoptosis in humans: A systematic review.

This review analyses the influence of acute running and cycling exercise on T lymphocyte apoptosis. We included randomized controlled trials (RCTs) and non-randomized case-control studies (NRCTs) measuring apoptosis by flow cytometry. Cochrane Library, Scopus, PubMed and Ovid were searched for running and cycling intervention studies. Risk of bias was assessed by Cochrane Collaboration's tools. We included five NRCTs and one RCT with a total of 93 participants. The RCT found a higher percentage of apoptotic T helper cells identified by upregulation of Annexin V, caspase-3 and caspase-9 under hypoxic conditions, and only one NRCT reported a higher percentage of highly differentiated apoptotic T cells immediately after exercise. Three hours after exercise, the same NRCT showed an increase in several T cell subsets such as T helper, cytotoxic T, low differentiated and regulatory T cells. The interventions were very heterogeneous by exercise protocol and external conditions. High risk of bias in NRCTs restricts accuracy of the included studies. Imprecision due to the small sample size limits further evidence. In the future, scientists should include apoptotic measures into their research design, plan RCTs, measure apoptosis at different time points post-exercise and increase sample size.