Can Building Muscle Mass Fortify the Strength of T Cells?

A new mouse study links more muscle mass with stronger CD8+ T cell response.

Posted Jun 16, 2020

 ra2 studio/Shutterstock
Source: ra2 studio/Shutterstock

A new study in mice has identified a possible link between increasing muscle mass and boosting immune system (CD8+ T cell) response. These findings (Wu et al., 2020) from the German Cancer Research Center's T Cell Metabolism Group led by Guoliang Cui were published on June 12 in the journal Science Alerts.

Before diving into the details of this animal study, it's important to state a few disclaimers right out of the gate: These preliminary findings show initial evidence that there may be a correlation between increased skeletal muscle mass and a stronger immune system in mice, not humans. To date, there have not been any human studies on the possible link between increased muscle mass and improved CD8+ T cell function.

Therefore, it would be premature for anyone to jump to the conclusion that pumping iron and building muscle mass is guaranteed to make his or her immune system stronger. Also, please do not interpret this research as implying that lifting weights or bulking up is an effective prophylaxis against COVID-19. This mouse study was initiated before the coronavirus disease 2019 (SARS-CoV-2) pandemic.

Although there are countless other scientifically-validated reasons to lift weights and maintain lean muscle mass across one's lifespan, it's too early to know for sure if this research in mice applies to humans. As senior author, Guoliang Cui, explains in a news release: "In our study, mice with more muscle mass were better able to cope with chronic viral infection than those whose muscles were weaker. But whether the results can be transferred to humans, future experiments will have to show."

How Do Skeletal Muscles Offset CD8+ T Cell Exhaustion in Mice? 

Much like an endurance athlete or marathon runner "bonks" and hits the wall, CD8+ T cells become exhausted when they're working hard to fight off a viral invader or kill cancer cells. 

When CD8+ T cells are activated to fend off virus-infected cells or a cancerous tumor, it can trigger a "cytokine storm" of inflammation. The latest study by Wu et al. suggests that muscle tissue provides a "T-cell shelter" from this inflammatory storm.

In a recent Frontiers in Immunology review article (Moro-Garcia et al., 2018), the authors describe cytokine storm pathology:

"Inflammation associated with a cytokine storm begins at a local site and spreads throughout the body via the systemic circulation. Redness, swelling or edema, heat, pain, and loss of function are the hallmarks of acute inflammation. When localized in skin or other tissue, these responses increase blood flow, enable vascular leukocytes and plasma proteins to reach extravascular sites of injury, increase local temperatures (which is advantageous for host defense against bacterial infections), and generate pain, thereby warning the host of the local responses."

In mice who were fighting off a chronic infection in the recent (Wu et al., 2020) experiment, increased muscle mass appeared to enhance the production of interleukin 15 (IL-15), which acts as a chemical messenger that opens the door for CD8+ T cells to take refuge in skeletal muscle tissue.

If CD8+ T cells are spatially sheltered from chronic inflammation inside muscle tissue, they appear to maintain their strength and don't become exhausted. As the authors explain: 

"Spatial compartmentalization is one mechanism to create diverse microenvironments in the immune system and to enable various immune cell differentiation pathways. Our study suggests that inflammatory cytokines are not evenly distributed among the skeletal muscles and lymphoid organs. The spatial compartmentalization of one population of CD8+ T cells in the relatively uninflamed microenvironment of the skeletal muscle shelters those T cells from systemic inflammation."

"If the T cells, which actively fight the infection, lose their full functionality through continuous stimulation, the precursor cells can migrate from the muscles and develop into functional T cells," first author, Jingxia Wu added. "This enables the immune system to fight the virus continuously over a long period."

When someone's immune system is fighting off a chronic infection or cancer, CD8+ T cells need to stay strong and active for extended periods of time. Unfortunately, patients who are battling cancer or other severe illness often experience wasting syndrome called "cachexia," which is marked by severe weight loss and muscle atrophy. This research suggests that losing muscle mass may create a double whammy for the immune system by not giving CD8+ T cells a haven from systemic inflammation.

Now that scientists at the German Cancer Research Center have identified how skeletal muscles provide a shelter for C8+ T cells, the next step is to see if there's a way to offset wasting syndrome and muscle atrophy, which might help the immune system stay strong and create an upward spiral of recovery. "These future studies, together with the current one, will enhance the understanding of the molecular mechanisms through which chronic infection—and cancer-associated cachexia influences antiviral and antitumor immunity," the authors conclude.

References

Jingxia Wu, Nina Weisshaar, Agnes Hotz-Wagenblatt, Alaa Madi, Sicong Ma, Alessa Mieg, Marvin Hering, Kerstin Mohr, Tilo Schlimbach, Helena Borgers, Guoliang Cui. "Skeletal Muscle Antagonizes Antiviral CD8+ T Cell Exhaustion." Science Advances (First published: June 12, 2020) DOI: 10.1126/sciadv.aba3458