Investigating the impact of single bouts of exercise on the number and function of peripheral blood immune cells

Pradana, Fendi ORCID: 0000-0003-2536-8613 (2024). Investigating the impact of single bouts of exercise on the number and function of peripheral blood immune cells. University of Birmingham. Ph.D.

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Abstract

Single bouts of exercise elicit changes to the number of immune cells within the bloodstream of humans. The initial transient increase in cell types including haemopoietic and progenitor cells (HSPCs) may offer relevance in the context of peripheral blood stem cell donations, which are used to collect HSPCs to treat various haematological disorders. The composition of the collected HSPC-rich immune graft is equally important, with higher numbers of cytolytic natural killer (NK) cells predicting better health outcomes in patients, and strikingly, these cells are mobilised up to 10fold during exercise. Mobilisation of immune cells during exercise forms part of a dynamic response in recovery, that may drive immune remodelling when repeated over time. The mechanisms underpinning this are not well understood, but recent work has started to examine bioenergetic responses within the total peripheral blood mononuclear cell (PBMC) fraction. PBMCs are a highly heterogeneous population of T and B lymphocytes and monocytes, each with various subsets with distinct bioenergetic profiles. Given that single bouts of exercise evoke marked compositional changes to PBMCs, providing single cell resolution of immunometabolic changes is crucial to facilitate understanding of the acute immune response to exercise.

Chapter 2 investigated differences in HSPC and cytolytic NK cell concentrations during and after continuous and interval-based cycling bouts utilising high intensity interval exercise (HIIE). We demonstrated that 2 x 2-minute bouts of HIIE (90-95% HRmax ) were sufficient to increase peripheral blood HSPC concentrations above rest, but not in response to 30 minutes of continuous cycling at moderate intensity. Furthermore, peripheral blood was enriched with higher numbers of cytolytic NK cells following bouts of high and low volume HIIE, compared to moderate intensity cycling. These data indicate that a very low volume of cycling at a high intensity can potentiate peripheral blood HSPC concentrations and provides a rationale for exploring whether intermittent cycling during PBSC collections can increase the yield of HSPCs for transplant.

Chapter 3 developed methods using extracellular flux analysis to examine the metabolic phenotype and real time responses to ex vivo activation of enriched naïve Helper and Cytotoxic T cells vs. PBMCs. Conditions were optimised for nutrient assay conditions (i.e., glucose and glutamine concentrations) and blood collection procedures (anticoagulant and blood ‘sitting’ time) to provide a robust experimental model for chapter 4 of this thesis.

Chapter 4 utilised an innovative human study design and methodology to investigate the impact of prolonged moderate intensity cycling on the energy metabolism of naïve T cells. This study provided detailed analysis at the single cell level for both naïve CD4+ and CD8 + T cell subsets. This chapter showed that a 2-hour session of cycling at a moderate intensity (define by a power output that reaches 95% of the lactate threshold1) did not cause any changes in the metabolic profiles of naïve CD4 + and CD8 + T cells, or peripheral blood mononuclear cells (PBMCs), immediately after or 2 hours into recovery, compared to rest. This included comprehensive measures of mitochondrial respiration, glycolytic flux, and ATP synthesis rates. Furthermore, there were no differences in the bioenergetic responses to ex vivo activation of PBMCs or enriched naïve T cells based on sampling before, immediately after or 2 hours following cycling completion. These data indicate that the metabolism of PBMCs and naïve T cells are unaltered within 2 hours of prolonged moderate intensity cycling.

Overall, this thesis presents novel data on acute changes in circulating immune cell number and function within peripheral blood.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):