Dysfunctional Tissue Resident CD8 T Cells Have Opposite Effect on Elderly Patients

Mayo Clinic_James R. MartinJames R. Martin/Shutterstock

A study recently conducted at Mayo Clinic showed that dysfunctional Tissue Resident Memory (TRM) CD8 T cells are actually working against the elderly, reducing immunity and enabling residual chronic lung issues after respiratory infections such as COVID-19. 

Both COVID-19 and the flu can cause pneumonia and after-affects that are longer lasting in older individuals. The researchers set out to discover why this is, or more specifically, how the aged environment causes the immune system’s primary functions of repair and immune protection in the lungs to break down.

The study, led by Drs. Nick P. Goplen, Ph.D. and Jie Sun, Ph.D. in the Thoracic Disease Research Unit at Mayo Clinic, was conducted in mice models approximating teens and adults ages 70 and older. 

TRM cells, which reside throughout the body, typically promote robust antiviral immunity. The researchers did not find this to be the case in the older mice.

Compared to their youthful counterparts, they displayed an increase of dysfunctional influenza specific TRM cells.  The dysfunctional T cells provided less protection against these infections and allowed for the thickening and scarring of lung tissue. 

Goplen told BioSpace that the team wanted to find out how the immune system balances this collateral damage to the lung with its primary mission of providing long-term immune protection against re-infection. 

“Until our recent study, no one had investigated organ and molecular-level immune response months after virus clearance in connection with aging. In our work, we showed that aged lungs failed to return to a pre-infection state long after young lungs did, maintaining the heightened level of white blood cells which was reflected by global upregulation of gene activation in the aged relative to young lungs,” Goplen said.

The team’s next finding was related to the increase in older individuals of T cells known to kill virus-infected cells, called “killer CD8 T cells”.  

“Our research team supposed that because these aged lungs were loaded with a higher density of all immune cells following infection – especially CD8 killer T cells – relative to young lungs, that age might actually improve the ability to fight off a viral reinfection. However, despite the increased numbers of immune cells residing in the older lungs, they did not exhibit protective immunity,” Goplen said.

Since the CD8 cells were not functioning as expected, Goplen et al. isolated them to find out why, and discovered that dysfunction in the cells was causing them to have a reverse effect.

The results are pertinent to the current COVID-19 pandemic as they present a potential correlation between age and prior infection and T-cell mediated immunity to COVID-19 conferred by a vaccine.

“If the findings in the mice translate to human and COVID-19 vaccine response is similar to influenza vaccine response in humans with respect to age, yes we would expect 70+ year-olds would not get as much protection from the vaccine as younger individuals,” said Goplen, adding the caveat, “Influenza vs. COVID-19 are very different vaccine strategies so we don't know to what degree they are related given we don't know the particulars of response in COVID-19 vaccines relative to influenza where a lot is known.”

Goplen explained that the science community is waiting on the full data from the COVID-19 vaccine trials to determine this.

“We do not know to what extent the various ongoing trials are including elderly individuals at the same rate they are represented in the general population, so we are eagerly awaiting that data to determine if there is more work to do regarding immune-status (e.g. age) and tuning COVID-19 vaccine strategy with regards to above,” explained Goplen.

The team’s next study will be to determine if these excess CD8 T cells are making pulmonary diseases such as COVID-19 or influenza themselves worse.

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