Vaccine works against type 1 diabetes in mouse experiments

Researchers find self-regulating feature of immune system

Weakness can be a strength when it comes to keeping the immune system from attacking the body’s own cells, mouse experiments that use a new vaccine against type 1 diabetes reveal.

STRENGTH IN WEAKNESS A microscope image shows vaccine nanoparticles (black dots) interacting with weak T cells. New research shows that the nanovaccine causes weak T cells to stop the immune system from attacking insulin-producing cells in the pancreas. Y. Yang and P. Santamaria

The new research, published online April 8 in Immunity, describes previously unknown cells that keep the immune system in check. The study demonstrates that the immune system is already outfitted with tools that can defuse destructive autoimmune reactions without damaging the body’s ability to fight infections. And it suggests that harnessing those tools may be a successful strategy for developing a vaccine for type 1 diabetes in humans.

In type 1 diabetes, also known as juvenile diabetes, white blood cells called T-cells attack insulin-producing beta cells in the pancreas. This type of self-destructive behavior is also at the root of diseases such as lupus, rheumatoid arthritis and multiple sclerosis.

Despite knowing for decades what causes the type 1 diabetes, “we haven’t been able to come up with a strategy that will selective blunt autoimmunity without impairing the immune system in general,” says study leader Pere Santamaria, an immunologist and geneticist at the Julia McFarlane Diabetes Research Centre at the University of Calgary in Canada. The new research reveals one way that healthy immune systems keep themselves from attacking the body’s own cells.
In one sense the immune system is like a cellular commando unit with some members that specialize in identifying threats, and others specialize in wiping them out.

Antigen-presenting cells are the intelligence operatives. They cruise around compiling information about invading microbes by sucking up bits of protein left in the debris of past battles. Then they hand information about those proteins to T cells, which go around looking for any cells that fit the description and kill them.

But sometimes, even in healthy people, proteins from the body’s own cells get picked up and put on the hit list. Normally, the immune system quickly realizes its mistake and stops attacking the body. But people with diabetes and other autoimmune disorders don’t seem to dispel the false threat.

The new study shows for the first time how a healthy immune system turns off the autoimmune attack. “It brings together a lot of threads that have been going through autoimmunity research for the past 20 years, but had never been tied together,” says Nikolai Petrovsky, director of endocrinology at Flinders Medical Centre in Adelaide, Australia.

Santamaria and his colleagues developed a nanovaccine consisting of a nanoparticle coated with proteins called major histocompatability complexes, or MHC, and with bits of protein from beta cells.

The vaccine caused one class of T cells to turn against the antigen-presenting cells that were identifying beta cells as enemies. Basically, the T cells were shooting the messengers before the hand-off of orders to exterminate the beta cells.

These T cells, called weak T cells or memory-like autoregulatory CD8+ cells, had been noticed before. But researchers didn’t think the cells played much of a role in the immune system, Santamaria says. Now it seems that by keeping false profiles out of the hands of other, strong T cells, the weak cells end the self-attack that causes diabetes.

“It’s as if you’ve taken one platoon of soldiers and turned them into pacifists, and they go and convince the rest of the army to stop firing,” Petrovsky explains.

Mice that are genetically predisposed to develop diabetes were protected from the disease if given the nanovaccine before becoming diabetic. Mice that were already diabetic when they got the nanovaccine were able to recover from the disease, the team reports. Nanovaccines against type 1 diabetes in humans may be ready for trials in two years, Santamaria says.

Other studies have shown that autoimmunity is much easier to turn off in mice than in people, but Petrovsky says the strategy is still worth trying in humans. And the new insight the study gives into the immune system may lead to improved therapies for a number of other autoimmune diseases as well.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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