New Clue to the Curious Case of Our Aging Immune System

A WEHI study may help solve a long-standing mystery: why a key immune organ in our bodies shrinks and loses function as we age. The thymus is an organ essential to good health because of its ability to produce special immune cells that are responsible for fighting infections and cancer.

In a world first, researchers have discovered new cells that drive this aging process in the thymus. These important findings could pave the way for restoring thymus function and preventing our immunity from weakening as we age.

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

The thymus is a small but powerful organ located behind the breastbone. It is the only organ in the body capable of producing T lymphocytes.

But a curious feature of the thymus is that it is the first organ in our body to shrink as we age. As it does, the T-cell growth areas of the thymus are replaced by fatty tissue, which decreases T-cell production and contributes to a weakened immune system.

Although the thymus is capable of regenerating itself after damage, researchers have yet to understand how to unlock this ability and boost immunity in humans as we age.

Professor Daniel Gray, director of the WEHI laboratory, said the new findings, published in Natural immunologycould help solve this mystery that has baffled researchers for decades.

“The number of new T cells produced in the body declines dramatically after puberty, regardless of your fitness. By age 65, the thymus is virtually retired,” Professor Gray said.

“This weakening of the thymus makes it harder for the body to cope with new infections, cancers and regulate immunity as we age.

“This is also why adults with weakened immune systems, for example due to cancer treatment or stem cell transplants, take much longer to recover than children.

“These adults take years to recover their T cells – or sometimes never do – putting them at higher risk of developing life-threatening infections for the rest of their lives.

“Exploring ways to restore thymic function is critical to finding new therapies that can improve outcomes for these vulnerable patients and finding a way to ensure that a healthy level of T cells are produced throughout our lives.”

The new study, the result of an international collaboration with groups at Fred Hutch Cancer Center (Seattle) and Memorial Sloan Kettering Cancer Center (NYC), provides crucial new information that could help achieve this goal.

“Our discovery offers a new perspective on thymic regeneration and immune restoration, and could reveal a way to boost immune function in vulnerable patients in the future,” Professor Gray said.

Scarring effects

Using advanced imaging techniques at WEHI’s Dynamic Imaging Center and animal models, the research team discovered two new cell types that cause the thymus to lose function.

These cells, which appeared only in the defective thymus of older mice and humans, formed clusters around areas where T cells grow, impairing the organ’s ability to produce these important immune cells.

The researchers found that these clumps also formed “scars” in the thymus, preventing the organ from restoring itself after damage.

Dr Kelin Zhao, who led the imaging efforts, said the results showed for the first time how this scarring process acts as a barrier to thymic regeneration and function.

“Although much of the research on thymic loss of function has focused on the shrinkage process, we have shown that changes that occur inside the organ also impact its ability to function with age,” Dr. Zhao said.

“By capturing these clumps of cells in the act and showing how they contribute to loss of thymic function, we were able to do something that no one else has ever done before, thanks in large part to the incredible advanced imaging platforms we have at WEHI.

“This knowledge allows us to determine whether these cells can be targeted therapeutically in the future, to help reverse the aging process of the thymus and boost T cell function in humans as we age. This is the goal our team is working toward.”