Can Your Immune System Be Rejuvenated? Yes, Says New Research

(Posted on Thursday, April 25, 2024)

During the recent Covid-19 pandemic, the rate of serious illness and death was jarringly high in older populations. Why? Weakening immune systems — as we age, we become more vulnerable to infections, and the effectiveness of vaccination drops. New research suggests we may be able to reverse the trend. By targeting abnormal stem cells using antibodies, a team of Stanford scientists was able to turn back the clock on mice’s immune systems, strengthening their reactions to viral threats and reducing overall inflammation. 

Immune Function and Blood Stem Cells: What’s the Connection?

We have two major types of blood cells: red and white. Red blood cells are primarily in charge of ferrying oxygen from the lungs to all of the tissues and organs in the body. White blood cells, on the other hand, are key players in the immune system. This includes all the usual big hitters: antibody-producing B cells, pathogen-busting T cells, debris-clearing macrophages, and so on. 

Both red and white blood cells, despite their different functions, come from the same source, called blood stem cells. These are special “precursor” cells, meaning they can develop into any kind of blood cell, whether red or white. Their job is to make sure the body’s supply of blood cells remains topped up at all times; as with most cells in the body, blood cells wear out with time and need to be replaced continuously. 

When we are young, our body does a good job of replenishing our blood cells as needed. But the older we grow, the more unsteady this process becomes. Not only does production slow, it also becomes increasingly unbalanced: the stem cells start developing a bias, preferentially morphing into certain kinds of blood cells over others. 

This bias comes at the expense of white blood cells, or immune cells, associated with the adaptive branch of our immune system. In particular, B and T cells, which are immune specialists that form highly specific responses to each pathogen they encounter. They also have the ability to remember previously encountered pathogens, allowing them to strike quickly and precisely in case of reinfection. It is this memory that grants us lasting protection against common pathogens. 

Instead of replenishing T and B cells, the aged body favors different immune cells, including monocytes, macrophages, and neutrophils. These make up a generalized branch of the immune system called innate immunity, which doesn’t distinguish between pathogens and instead depends on a blanket response. Think of these cells as the first line of defense — clumsier and brutish, but reliable. These immune cells are also known to crank up inflammation as part of their strategy. In short bursts, this is fine, but over extended periods, it can cause damage to surrounding cells and tissues, a little like that one spoiled fruit that causes the rest of the bowl to go bad. 

Rebalancing the Scales

This trend of “exhausted” blood stem cells that develop a bias against B and T cells has been observed not only in older mice but in humans as well. Scientists speculate that it weakens the corresponding antibody and T-cell responses of the immune system, which would help explain why older adults are more susceptible to respiratory viruses and other such illnesses. 

If the immune dysfunction seen in older adults can be traced back to an imbalance in blood cells, then shouldn’t “rebalancing” them rejuvenate the immune system too? Easier said than done. Although we know that blood stem cells develop a bias in old age, we still don’t know the exact mechanisms by which this happens, making it difficult to reverse the process. 

The team of scientists at the Weissman Lab came up with a nifty idea to circumvent this issue: bespoke antibodies that attach to the imbalanced blood stem cells and destroy them. This way, instead of having to reverse the process as a whole, they simply get rid of the troublesome blood stem cells before they can cause any imbalances. 

But antibodies require some kind of landmark to help them locate and attach to their intended target — like lock and key, each antibody has a corresponding receptor on a cell’s surface that it homes onto. Crucially, the researchers would have to find cell-surface receptors that were only present on the exhausted blood stem cells that disproportionately develop into innate immune cells. Otherwise, they would risk eliminating all blood stem cells, including the normal, balanced ones. 

To find potential landmarks to guide their engineered antibodies, the researchers scoured large transcription databases. They eventually found three promising candidate proteins that were common on the surface of the exhausted blood stem cells but not on the surface of their normal counterparts. 

Next, they infused their antibodies into older mice to see whether they would have the desired effect. Indeed, the treated mice were able to hold off viral infections much more successfully than older mice that had not received the antibody treatment. The group that received the antibodies also mounted a far stronger response to vaccination. Chronic low-level inflammation was also reduced. 

The immune benefits were confirmed at the molecular level, where treated mice had fewer imbalanced blood stem cells. There was also a noticeable uptick in the production of B and T cells that lasted up to four months after the treatment. In short, their immune systems had been rejuvenated. 

Implications

We depend on our immune system every minute of every day; it is always busy at work, protecting us from foreign invaders and threats. Aging weakens the immune system, leaving us vulnerable to infections we would usually be able to fight off without much trouble. It reaches a point where catching the flu becomes a life-threatening event. 

This latest study suggests we may soon have a way of rejuvenating our immune system, bringing it back to full strength. Although these initial tests were performed in mice, the researchers are already looking ahead and hopeful that the same approach will work in humans. Still, it’s safe to assume it will take a number of years before this treatment option becomes approved for human use. And more still for it to become widely available.