A-beta injected into half of a mouse's brain slowly incites other A-beta molecules to accumulate, Prusiner and colleagues reported earlier this year (SN: 7/14/12, p. 5). And Swedish scientists caught A-beta jumping directly from nerve cell to nerve cell in rat and human cells in a dish, suggesting that the protein can follow neural connections in the brain.

Still more evidence comes from a study on a particularly dangerous form of A-beta. In "€œvanishingly small"€ quantities, this form, called pyroglutamylated A-beta, can cause normal versions of A-beta to turn deadly, says study coauthor George Bloom of the University of Virginia. These proteins needed just 24 hours to kill half of mouse nerve cells tested in a dish (SN: 6/2/12, p. 18).

When we learn something new, our neurons tear down old connections and build new ones. In the process they cast off lots of molecules. To the immune system, this waste may look like an infection or some other kind of trouble, resulting in inflammation and the release of harsh compounds that normally fight viruses but can also interfere with the brain and its function. Kipnis suggests that T cells keep this process in check, differentiating between disease and ordinary stress and, when warranted, telling other immune cells to stand down by releasing antagonist molecules that prevent misguided inflammation.

The same T cells that protect the brain from inflammation also work to keep us sharp; and in what appears to be a feedback loop, the mere act of learning reinforces the effect. As mice learn something new, T cells in the meninges produce high levels of a molecule called interleukin 4 (IL-4). IL-4 is an immune system signal that curbs the inflammatory response and, according to research by Kipnis and others, also improves learning. Indeed, when mice lacking the gene for making IL-4 take the water maze test, they do badly, perhaps because their T cells lack a critical signal involved in fast learning.

This theory could explain why we lose our mental edge when we get sick, Kipnis says. When we’re healthy, T cells keep the immune cells in the meninges from inflaming the brain. But when we get sick, the T cells loosen their hold to let the immune system attack invading pathogens. The resulting inflammation helps clear out the invaders, but it also blunts learning. When we’re sick, Kipnis proposes, it’s more important to launch a powerful immune attack than to have a sharp mind. “Everything in life is priorities,” he says.

Kipnis has recently started to investigate what happens to people’s brains when they start losing T cells. People with cancer, for example, often suffer a loss of T cells when they undergo chemotherapy. It may be no coincidence, he argues, that chemotherapy is notorious for causing “chemo brain”—a fuzzy mental state in which patients have trouble thinking clearly. Kipnis proposes that without T cells to keep inflammation in check, immune cells in the meninges pump harmful compounds into the brain.

Old age also strips us of our T cells. The thymus, a strawberry-size gland in the chest, produces a steady stream of T cell precursors in our youth. But over the decades it shrinks until it’s barely visible. Kipnis proposes that with fewer T cells, older people cannot effectively suppress the inflammation around their brains—which could play a part in the cognitive decline that people experience as they age.

An experiment Kipnis and his colleagues carried out recently on mice missing T cells foreshadows how future brain-immune medicine might work. The scientists drew blood from old mice, whose supply of T cells was depleted, and isolated immune cells. They added IL-4 to the flasks where they reared those immune cells. Then the scientists injected the IL-4-exposed cells back into the mice. Afterward, the mice were able to learn well—presumably because their brains were no longer suffering from inflammation.