Investigating the role of immune checkpoints in the regulation of T-cell activity

"Immune checkpoint receptors, such as Programmed-Death Receptor-1 (PD-1) and Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) are critical negative regulators of T-cell activity that prevent collateral immunological damage and promote self-tolerance. Low expression of these receptors initiates a heightened state of T-cell activation that drives aberrant migration of T-cells into tissues and has been strongly linked to autoimmune disease. However, mechanistic studies in humans are sparse in this area, as well as an understanding of the lifestyle factors that drive these immune responses, which are crucial for maintaining long-term health.
Preliminary data from our laboratory suggests that exercise can increase the circulating concentration of T-cells expressing PD-1, as well as increasing the expression of PD-1 within each T-cell. We suggest that being more physically active throughout the lifespan may be an effective strategy to boost immune checkpoint receptor expression on immune cells, thus controlling the activation and migration of immune cells into tissues and maintaining immune system health.
The current study will investigate the effect exercise has on immune checkpoint receptor expression and will explore the role immune checkpoints play in regulating T-cell activity. To do this, exercise intervention trials will be performed by healthy adults and those with autoimmune diseases such as type-1-diabetes and systemic lupus erythematosus. Participant samples will then be analysed using techniques including flow cytometry, ELISA, tetramer assays, and ex vivo functional T-cell assays. By examining the role of immune checkpoint receptors in governing functional responses, we can better understand how exercise helps to maintain immune system health. "