Killer T Cells Invade the Aging Brain and Disrupt Generation of New Neurons
The blood-brain barrier is a lining of specialized cells wrapping blood vessels, in place to keep the central nervous system isolated from the rest of the body. Unfortunately, and like all aspects of our biology, the blood-brain barrier becomes dysfunctional with age, and this allows cells from other parts of the body to infiltrate the brain. As the research results here demonstrate, this is particularly problematic in the case of immune cells that should not normally be present in the brain. By generating inflammatory signals, these invading cells can disrupt vital activities of neurons or the stem cells responsible for generating new neurons.
Many a spot in a young mammal's brain is bursting with brand new neurons. But for the most part, those neurons have to last a lifetime. Older mammals' brains retain only a couple of neurogenic niches, consisting of several cell types whose mix is critical for supporting neural stem cells that can both differentiate into neurons and generate more of themselves. New neurons spawned in these niches are considered essential to forming new memories and to learning, as well as to odor discrimination.
In order to learn more about the composition of the neurogenic niche, researchers catalogued, one cell at a time, the activation levels of the genes in each of nearly 15,000 cells extracted from the subventricular zone (a neurogenic niche found in mice and human brains) of healthy 3-month-old mice and healthy 28- or 29-month-old mice. When the researchers compared their observations in the brains of young mice (equivalent in human years to young adults) with what they saw in the brains of old mice (equivalent to people in their 80s), they identified a couple of cell types in the older mice not typically expected to be there - and barely present in the young mice. In particular, they found immune cells known as killer T cells lurking in the older mice's subventricular zone.
The healthy brain is by no means devoid of immune cells. In fact, it boasts its own unique version of them, called microglia. But a much greater variety of immune cells abounding in the blood, spleen, gut and elsewhere in the body are ordinarily denied entry to the brain, as the blood vessels pervading the brain have tightly sealed walls. The resulting so-called blood-brain barrier renders a healthy brain safe from the intrusion of potentially harmful immune cells on an inflammatory tear as the result of a systemic illness or injury.
Further experiments demonstrated several aspects of the killer T cells' not-so-mellow interaction with neural stem cells. For one thing, tests in cell cultures and in living animals indicated that killer T cells isolated from old mice's subventricular zone were far more disposed than those from the blood of the same mice to pump out an inflammation-promoting substance that stopped neural stem cells from generating new nerve cells. Second, killer T cells were seen nestled next to neural stem cells in the subventricular zones of old mice and in tissue taken from the corresponding neurogenic niche in autopsied brains of old humans; where this was the case, the neural stem cells were less geared up to proliferate.