New clues about the strange phenomenon of the aging immune system

The thymus is an organ essential to health due to its ability to produce specialized immune cells that play a role in fighting infection and cancer.

For the first time, researchers have identified new cells in the thymus that promote this aging process, an important discovery that could lead to methods for restoring thymus function and preventing the decline of immunity with age.

At a glance

• The thymus is an essential organ for immune defense, but it atrophies and weakens with age, and the cause of this decline has long remained a mystery.
• A new study provides the first visualisation of how two types of cells drive this ageing process, causing the thymus to lose its function and regenerative capacity over time.
• This discovery could help find ways to stop thymus ageing and, importantly, potentially develop ways to restore immunity in immune-compromised people.

T cells, also known as T lymphocytes, are a type of white blood cell that play a key role in the immune system. T cells are essential for identifying and responding to pathogens such as viruses and bacteria, and for eliminating infected and cancerous cells.

The thymus is a small but powerful organ located behind the breastbone. It is the only organ in the body that can make T cells.

However, an interesting feature of the thymus is that it is the first organ in the body to atrophy with age. When this happens, areas of T cell proliferation in the thymus are replaced by fatty tissue, leading to reduced T cell production and a weakened immune system.

The thymus has the ability to regenerate from injury, but so far researchers have not been able to figure out how to unlock this ability to boost human immunity as we age.

Professor Daniel Gray of the WEHI Institute said: Nature Immunologymay help solve a mystery that has puzzled researchers for decades.

“Regardless of fitness, after puberty the number of new T cells produced by the body drops off dramatically and by the age of 65 the thymus gland has effectively degenerated,” Prof Gray said.

“As we age, a weakened thymus makes it harder for the body to fight new infections and cancers and regulate the immune system.

“This is also why adults who have a weakened immune system, for example after cancer treatment or a stem cell transplant, take much longer to recover than children.”

“These adults can take years to recover their T cells, and sometimes they never do, putting them at increased risk of contracting potentially life-threatening infections for the rest of their lives.”

“Exploring ways to restore thymus function is important for finding new therapies that can improve outcomes for these vulnerable patients and ensure healthy levels of T cells are produced throughout their lives.”

The new study, an international collaboration between groups at Fred Hutch Cancer Center in Seattle and Memorial Sloan Kettering Cancer Center in New York, provides important new insights that may help achieve this goal.

“Our findings shed new light on thymus regeneration and immune restoration and may in future shed light on how to boost immune function in immunocompromised patients,” said Professor Gray.

Scar formation effect

Using advanced imaging techniques from WEHI's Dynamic Imaging Centre and animal models, the research team discovered two new cell types that cause loss of thymus function.

These cells were found to only appear in the defective thymus of older mice and humans, where they form clusters around areas of T cell development, compromising the organ's ability to generate these important immune cells.

In a world first, the researchers discovered that these clusters form a “scar” in the thymus, preventing it from recovering after injury.

Dr. Kelin Zhao, who led the imaging work, said the findings showed for the first time how the scarring process acts as a barrier to thymus regeneration and function.

“Research on thymus loss of function has mainly focused on the thymus atrophy process, but we have demonstrated that changes occurring within the thymus also affect thymus function with age,” said Dr. Zhao.

“By capturing these cell clusters in situ and showing how they contribute to the loss of thymus function, we've been able to do something that nobody has been able to do before, and this is thanks in large part to the incredibly advanced imaging platform that we have at WEHI.”

“This knowledge will enable us to investigate whether these cells could be targeted therapeutically in the future to reverse the aging thymus and boost T cell function in humans with age, which is the goal our team is working towards.”