From the Guidelines
T cell fitness in the context of cell modification (cellmod) is crucial for effective immunotherapy, and exercise has been shown to have a positive impact on regulatory T cells, which can improve immunomodulation and overall T cell fitness 1. To optimize T cell fitness during cellmod procedures, it is essential to consider the effects of exercise on regulatory T cells.
- Exercise can induce a decline in senescent or exhausted T cells, making space for newly built, naive T cells, which can improve immunocompetence 1.
- The immunomodulatory characteristics of exercise may account for some health-promoting effects, including the long-term establishment of a more anti-inflammatory state on the systemic level 1. When modifying T cells, it is recommended to use a combination of IL-2 and IL-7 in culture media, maintain cells at lower densities, and include human serum rather than FBS.
- The modification process should be completed within 24-48 hours to minimize ex vivo culture time, and cells should be cryopreserved in a solution containing 10% DMSO with 90% human serum albumin if not used immediately.
- During expansion, consider adding IL-15 to promote memory T cell development. T cell fitness is determined by metabolic activity, with naive and memory T cells relying on oxidative phosphorylation while effector T cells depend on glycolysis.
- Preserving this metabolic flexibility during cellmod ensures better persistence and function after infusion.
- The culture conditions should include glucose and glutamine to support both metabolic pathways. Monitoring expression of exhaustion markers like PD-1, LAG-3, and TIM-3 throughout the process can help assess T cell quality before therapeutic use. However, the effects of exercise on T cell fitness and cellmod are not fully understood, and more research is needed to determine the optimal exercise interventions and cellmod procedures to improve T cell fitness and overall immunotherapy outcomes 1.
From the Research
T Cell Fitness and CellMod
- T cell fitness is crucial in maintaining immune homeostasis and preventing autoimmune diseases 2
- CellMod, or cellular modification, can be used to enhance T cell function and treat autoimmune diseases 3, 4, 5
Mechanisms of T Cell Regulation
- T-regulatory cells (Tregs) play a key role in maintaining immune tolerance and preventing autoimmune diseases 3, 6, 5
- Tregs can be used therapeutically to treat autoimmune diseases, either through adoptive transfer or by enhancing their function in vivo 3, 5
Applications of T Cell Vaccination
- T cell vaccination (TCV) has been shown to be effective in treating autoimmune diseases by eliminating autoreactive T cells 4
- TCV has been tested in several animal models and clinical trials, with promising results 4