Functional characterisation of CD8+ T cells mobilised with acute supramaximal high-intensity interval exercise [...], 2025, Strömberg et al

[forestglip]

Functional characterisation of CD8+ T cells mobilised with acute supramaximal high-intensity interval exercise: implications for immune surveillance

Anna Strömberg, Mirko Mandić, Brennan J Wadsworth, Sebastian Proschinger, Seher Alam, Lisa MJ Eriksson, Laura Barbieri, Eric Rullman, Helene Rundqvist

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Objectives
The beneficial influence of exercise on outcomes such as infection control and cancer prevention has been attributed partly to the immune system response during physical exertion. CD8+ T cells play a crucial role in immune surveillance, and in this study, we performed an in-depth analysis of the impact of supramaximal high-intensity exercise (HIIT) on CD8+ T-cell dynamics and function, which are currently lacking in the literature.

Methods
CD8+ T cells obtained from healthy human subjects before and after 3 × 30 s of HIIT were analysed ex vivo for viability and expansion properties, metabolic function using SeaHorse, IFN-gamma release using EliSpot, phenotype using RNA-seq and flow cytometry, and cytotoxic capacity by co-culture with HEK293T cells.

Results
Exercise led to a threefold increase in CD8+ T-cell count, and CD8+ T cells obtained after exercise had a more cytotoxic profile.

Post-exercise CD8+ T cells had a lower glycolytic capacity than pre-exercise cells, and incubation of pre-exercise CD8+ T cells with post-exercise serum replicated this metabolic shift, suggesting a systemic effect of exercise on CD8+ T-cell metabolism.

Importantly, CD8+ T cells maintained their viability and expansion properties despite the metabolic challenges induced by exercise.

Functionally, post-exercise CD8+ T cells showed increased release of IFN-gamma and an enhanced unspecific cell killing capacity as demonstrated by co-culture with the immortalised cell line HEK293T.

Conclusion
The pronounced increase in the total number of circulating CD8+ T-cells with an increased cytotoxic capacity suggests a potential improvement in immune surveillance after acute HIIT.

Link | PDF (Clinical and Translational Immunology) [Open Access]

 

[V.R.T.]

Functional characterisation of CD8+ T cells mobilised with acute supramaximal high-intensity interval exercise: implications for immune surveillance

Anna Strömberg, Mirko Mandić, Brennan J Wadsworth, Sebastian Proschinger, Seher Alam, Lisa MJ Eriksson, Laura Barbieri, Eric Rullman, Helene Rundqvist

Objectives
The beneficial influence of exercise on outcomes such as infection control and cancer prevention has been attributed partly to the immune system response during physical exertion. CD8+ T cells play a crucial role in immune surveillance, and in this study, we performed an in-depth analysis of the impact of supramaximal high-intensity exercise (HIIT) on CD8+ T-cell dynamics and function, which are currently lacking in the literature.

Methods
CD8+ T cells obtained from healthy human subjects before and after 3 × 30 s of HIIT were analysed ex vivo for viability and expansion properties, metabolic function using SeaHorse, IFN-gamma release using EliSpot, phenotype using RNA-seq and flow cytometry, and cytotoxic capacity by co-culture with HEK293T cells.

Results
Exercise led to a threefold increase in CD8+ T-cell count, and CD8+ T cells obtained after exercise had a more cytotoxic profile. Post-exercise CD8+ T cells had a lower glycolytic capacity than pre-exercise cells, and incubation of pre-exercise CD8+ T cells with post-exercise serum replicated this metabolic shift, suggesting a systemic effect of exercise on CD8+ T-cell metabolism. Importantly, CD8+ T cells maintained their viability and expansion properties despite the metabolic challenges induced by exercise. Functionally, post-exercise CD8+ T cells showed increased release of IFN-gamma and an enhanced unspecific cell killing capacity as demonstrated by co-culture with the immortalised cell line HEK293T.

Conclusion
The pronounced increase in the total number of circulating CD8+ T-cells with an increased cytotoxic capacity suggests a potential improvement in immune surveillance after acute HIIT.

Link | PDF (Clinical and Translational Immunology) [Open Access]

Could this possibly explain why pwME get PEM and sometimes deteriorate after exercise?

I note IFN-G increase which is of course relevant to the Edwards/Cambridge/Cliff hypothesis.

 

[Utsikt]

Could this possibly explain why pwME get PEM and sometimes deteriorate after exercise?

If the shift in immune cells is temporary, how would it explain long term deterioration?

 

[V.R.T.]

If the shift in immune cells is temporary, how would it explain long term deterioration?

I guess I meant could it be a factor - this process going awry somehow. If ifn-g and cd8 t cells are the medium by which PEM is triggered during/after activity essentially.

And in terms of long term deterioration I don't know. I suppose I was thinking of this process as adding fuel to the fire, so to speak. As in it could be part of the feedback loop that causes deterioation after repeated PEM triggers. I suppose I was thinking of my own exercise induced deterioration.

 

[Hutan]

It makes sense that the body would react to substantial exertion by sending signals to now rest.

incubation of pre-exercise CD8+ T cells with post-exercise serum replicated this metabolic shift, suggesting a systemic effect of exercise on CD8+ T-cell metabolism.

And it is sounding as though those signals are sent through the blood.

In a recent study, we showed that exercise can increase infiltration of CD8+ T cells to the tumor microenvironment and thereby reduce neoplastic growth.<a href="https://onlinelibrary.wiley.com/doi/10.1002/cti2.70037#cti270037-bib-0007" data-tab="pane-pcw-references">7</a> Depletion of the CD8+ T-cell population abolished the beneficial effects of exercise, strongly associating the beneficial effects of exercise with the cytotoxic T-cell population. In addition, we found that metabolites secreted by the active muscle, such as lactate and TCA metabolites, increased T-cell expression of effector molecules and reduced the expression of surface molecules responsible for homing to lymphatic organs,<a href="https://onlinelibrary.wiley.com/doi/10.1002/cti2.70037#cti270037-bib-0007" data-tab="pane-pcw-references">7</a>, <a href="https://onlinelibrary.wiley.com/doi/10.1002/cti2.70037#cti270037-bib-0008" data-tab="pane-pcw-references">8</a> suggesting that exercise-induced metabolic perturbation can affect T-cell phenotype and function.

Audrey's study found that ME/CFS serum did not change the metabolism of muscle cells, but what if the missing ingredient was the T-cells? Could the different results of the Norwegian team be due to a different serum production process that retained some T-cells or functional molecules from t-cells?

Muscles seem to be secreting molecules that change T-cells, activating them to head out into the body, scanning for things to sort out. What if these activated T-cells cause the problems in people with ME/CFS? By interacting with neurons perhaps?

There are papers talking about resident populations of t-cells (resident memory cells) in the brain. And that these cells can be permanent changed by physical brain trauma. What if the signals from exerted muscles travel through the blood to those brain t-cells?

@chillier

 

[Jonathan Edwards]

Recruitment of CD8 T cells to muscle with exercise has been known about since the time when Jo Cambridge was doing her PhD around 1980. This paper may give a bit more detail on circulating cell function but I amnot sure it tells us much about what recruits the cells?

This was very much the subtext for our Qeios piece. The question is whether PEM relates to T cells that end up in muscle or whether there is circulating gamma interferon spilling out or whether T cells silently move around the body and only interact through cytokines with nervous tissue in brain or peripheral nerve.

Another question would be whether in ME/CFS a different subpopulation of T cells gets mobilised. Only CD8s go to muscle but there are lots of other subpopulations that might go other places in response to the original stimulus.