High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT?

Area of Science:

• Immunology
• Exercise Physiology
• Transplantation Medicine

Background:

• Adoptive transfer of virus-specific T cells (VSTs) is crucial for managing opportunistic viral infections post-transplantation.
• Low frequencies of circulating memory VSTs in donors limit the efficiency and purity of T-cell products, impacting treatment effectiveness.

Purpose of the Study:

• To compare the effects of high-intensity interval training (HIT) versus continuous exercise (CONT) on the frequency and function of circulating donor VSTs.
• To identify optimal timing for T-cell donation post-exercise by analyzing T-cell function, phenotype, activation, and proliferation.

Main Methods:

• A pilot cross-over trial comparing a 30-minute HIT bout with 30-minute CONT exercise.
• Immunoassays to assess donor cellular immunity, focusing on VSTs against Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), and Adenovirus (AdV).
• Evaluation of T-cell function, activation, and proliferation at various time points pre- and post-exercise; small-scale T-cell enrichment using IFN-γ cytokine secretion assay.

Main Results:

• HIT significantly increased VST response by up to fivefold compared to CONT.
• Donors with moderate fitness levels exhibited higher baseline and post-exercise VST frequencies than highly fit donors.
• Both exercise types enhanced VSTs against less immunodominant antigens (CMV, EBV, AdV) compared to immunodominant ones.

Conclusions:

• Exercise prior to T-cell donation positively impacts donor cellular immunity, increasing circulating functional VSTs.
• A single HIT session 24 hours before T-cell donation can substantially improve the manufacturing of clinically applicable VSTs.
• This simple, cost-effective adjuvant treatment is particularly effective for enhancing virus-specific memory T cells with low precursor frequencies.