As we age, our immune response tends to grow both hyperactive and unfocused, like a car with lousy brakes, a distracted driver and a brick on the gas pedal.
“The aging immune system becomes less focused — less capable of defending against cancers and infections or responding robustly to vaccinations — and much more inflammatory,” immunologist/rheumatologist Connie Weyand, MD, told me when I interviewed her for a news release on her latest study.
The study, published in the Journal of Clinical Investigation, describes the workings of an important type of immune cell whose existence was unknown just a few years ago — and whose failure could explain, at least in part, why our immune systems go increasingly haywire with advancing age. The study tied these cells' malfunction to at least one autoimmune disorder.
From my release:
When a pathogen invades the body or a cancerous cell emerges or a vaccine dose is administered, the immune system ramps up, producing antibodies and attacking suspected infected or tumorous cells, and secreting copious signaling substances that spur further attack-mode action.
Left unchecked, this chain reaction would result in chronic inflammation, which is exactly what seems to happen to most of us as we grow older.
Fortunately, there's a class of cells that acts as a brake on what could otherwise be a runaway immune response. The existence and importance of these cells — known as regulatory T cells, or Tregs (pronounced "Tee-regs") for short — have long been known. But in 2012, Weyand's team published their discovery of a novel subtype of Tregs called CD8 Tregs, whose special characteristics make them especially equipped to put the chill on other immune cells at risk of potential overdrive.
After figuring out numerous details of exactly how CD8 Tregs work, Weyand and her colleagues examined samples of healthy individuals' blood from the Stanford Blood Center and found that CD8 Tregs were only about half as common in blood from people ages 60 or older as in blood from 20- to 30-years-olds. Making matters worse, the immune-suppressing ability of the ones that stick around declines with advancing age.
At Stanford Health Care’s Immunology and Rheumatology Clinic, both Weyand and study co-author and fellow Stanford immunologist (and husband) Jorg Goronzy, MD, frequently see patients with various auto-inflammatory conditions in which immune cells gang up and attack vascular tissue — i.e., blood vessels. One such disease is giant-cell arteritis, or GCA, which affects large blood vessels (making it extremely dangerous) and in which inflammation is particularly fierce.
GCA is poorly understood. Fortunately, it's also rare. "It's an old Viking disease," Weyand (a world-renowned expert on the disorder) told me. "It's greatest incidence — about one in 10,000 new cases per year — is in Iceland."
Weyand, Goronzy and their associates showed that GCA patients’ immune brakes — their reserves of CD8 Tregs — are shot, leaving other, aggressive immune-cell types unpoliced.
The researchers have now begun to tally CD8 Tregs in patients with more widespread age-associated disorders understood to be driven by chronic inflammation, such as coronary artery disease and Alzheimer’s and Parkinson’s diseases, to see if CD8 Treg deficits are behind those, as well.
If so, the new findings about what makes CD8 Tregs' braking power wear out could go some distance toward discovering new treatments for these ravages of old age.
Previously: And one for the road: Why a single shot may not (always) be enough to stave off shingles, Glucose-guzzling immune cells may cook up coronary artery disease, Found: A molecule mediating memory meltdown in aging immune systems, Our aging immune systems are still in business, but increasingly thrown out of balance, How to amp up an aging immune response? and Age-related drop in immune responsiveness may be reversible
Photo by Nick Johnson
