COVID-19 vaccination produces exercise-responsive SARS-CoV-2-specific T-cells regardless of infection history

Purpose: The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) specific T-cells and neutralizing antibodies during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019 (COVID-19). We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter neutralizing antibody titers. Methods: 18 healthy participants completed a 20 min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine. All major leukocyte subtypes were enumerated before, during, and after exercise by flow cytometry, and immune responses to SARS CoV-2 were determined using whole blood peptide stimulation assays, T-cell receptor (TCR) sequencing, and SARS-CoV-2 neutralizing antibody serology. Results: COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise. However, noninfected participants had a significantly reduced mobilization of CD4+ and CD8+ naive T-cells, as well as CD4+ central memory T-cells, after vaccination (synthetic immunity group); this was not seen after vaccination in those with prior SARS CoV-2 infection (hybrid immunity group). Acute exercise after vaccination robustly mobilized SARSCoV-2 specific T-cells to blood in an intensity-dependent manner. Both groups mobilized T-cells that reacted to spike protein; however, only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens. Neutralizing antibodies increased significantly during exercise only in the hybrid immunity group. Conclusion: These data indicate that acute exercise mobilizes SARS CoV-2-specific Tcells that recognize spike protein and increases the redistribution of neutralizing antibodies in individuals with hybrid immunity

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice

BackgroundEvery bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer survivors. Our aim was to provide the first detailed single cell transcriptomic analysis of exercise-mobilized lymphocytes and test their effectiveness as a donor lymphocyte infusion (DLI) in xenogeneic mice engrafted with human leukemia.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from healthy volunteers at rest and at the end of an acute bout of cycling exercise. Flow cytometry and single-cell RNA sequencing was performed to identify phenotypic and transcriptomic differences between resting and exercise-mobilized cells using a targeted gene expression panel curated for human immunology. PBMCs were injected into the tail vein of xenogeneic NSG-IL-15 mice and subsequently challenged with a luciferase tagged chronic myelogenous leukemia cell line (K562). Tumor growth (bioluminescence) and xenogeneic graft-versus-host disease (GvHD) were monitored bi-weekly for 40-days.ResultsExercise preferentially mobilized NK-cell, CD8+ T-cell and monocyte subtypes with a differentiated and effector phenotype, without significantly mobilizing CD4+ regulatory T-cells. Mobilized effector lymphocytes, particularly effector-memory CD8+ T-cells and NK-cells, displayed differentially expressed genes and enriched gene sets associated with anti-tumor activity, including cytotoxicity, migration/chemotaxis, antigen binding, cytokine responsiveness and alloreactivity (e.g. graft-versus-host/leukemia). Mice receiving exercise-mobilized PBMCs had lower tumor burden and higher overall survival (4.14E+08 photons/s and 47%, respectively) at day 40 compared to mice receiving resting PBMCs (12.1E+08 photons/s and 22%, respectively) from the same donors (p<0.05). Human immune cell engraftment was similar for resting and exercise-mobilized DLI. However, when compared to non-tumor bearing mice, K562 increased the expansion of NK-cell and CD3+/CD4-/CD8- T-cells in mice receiving exercise-mobilized but not resting lymphocytes, 1-2 weeks after DLI. No differences in GvHD or GvHD-free survival was observed between groups either with or without K562 challenge.ConclusionExercise in humans mobilizes effector lymphocytes with an anti-tumor transcriptomic profile and their use as DLI extends survival and enhances the graft-versus-leukemia (GvL) effect without exacerbating GvHD in human leukemia bearing xenogeneic mice. Exercise may serve as an effective and economical adjuvant to increase the GvL effects of allogeneic cell therapies without intensifying GvHD

Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-beta, and TNF-alpha), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-beta; increased TNF-alpha (p <= 0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-alpha (r=-0.404, p=0.027; r=-0.427, p=0.019; and r=-0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.Department of Kinesiology and Health Sciences at Virginia Commonwealth UniversityOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Recent COVID-19 vaccination has minimal effects on the physiological responses to graded exercise in physically active healthy people

Athletes are advised to receive the COVID-19 vaccination to protect them from SARS CoV-2 infection during major competitions. Despite this, many athletes are reluctant to get the COVID-19 vaccine due to concerns that symptoms of vaccinosis may impair athletic performance. OBJECTIVE: To determine the effects of COVID-19 vaccination on the physiological responses to graded exercise. METHODS: Healthy physically active participants completed a 20-minute bout of graded cycling exercise at intensities corresponding to 50, 60, 70 and 80% of the pre-determined VO2max before and ~21 days after receiving the COVID-19 vaccine (2 dose Pfizer mRNA or 1 dose Johnson&Johnson). RESULTS: Vaccination had no effect on a large number of physiological responses to exercise measured in blood (e.g. lactate, epinephrine, cortisol) and by respiratory gas exchange (e.g. oxygen uptake, CO2 production, ventilation, respiratory exchange ratio, predicted VO2max, ventilatory threshold) (p>0.05). We did, however, find significant elevations in heart rate (~5 bpm) and norepinephrine (p = 0.006 and 0.04, respectively) in response to vigorous (e.g. 70-80% VO2max) intensity exercise after vaccination, particularly in those that received the two shot Pfizer mRNA vaccine regimen. These findings held true when compared to demographically matched controls who completed identical bouts of exercise several weeks apart without receiving a vaccine; delta values for heart rate (p=0.03) and norepinephrine (p=0.01) were elevated in the second trial for those that received the Pfizer mRNA vaccine compared to the controls at the 70% and 80% VO2max stages, respectively. CONCLUSION: Recent COVID-19 vaccination has minimal effects on the physiological responses to graded exercise in physically active healthy people. The small elevations in cardiovascular and neuroendocrine responses to exercise after the Pfizer mRNA vaccine regimen could have implications for athletes at the elite level and warrants investigation