Scientists have found new evidence to explain how food tolerance emerges over time in normal individuals, according to research published in Science.

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Allergies to peanuts and other foods affect young children more than adults.

Food allergies affect around 15 million Americans, including many children. Symptoms of allergies and intolerance can range from relatively minor, such as a harmless skin rash, to potentially fatal anaphylactic shock.

Many individuals outgrow their allergy as they reach adulthood. This is thought to be due to the immune system learning to tolerate food that it previously perceived as “foreign.”

Researchers from La Jolla Institute for Allergy and Immunology (LJI) in San Diego, CA, led by Charles Surh, PhD, wanted to explain why children, who have more limited exposure to novel foods than adults, are more prone to food allergies.

They hypothesized that consuming a normal diet would stimulate cells in the gut that prevent the immune system from rejecting food.

Food and pathogens both display macromolecular markers known as antigens. These antigens announce to the immune system that a food is “foreign.”

Mouse studies have previously looked at how the body would distinguish antigenic “friend” from “foe.”

The mice were fed with an egg protein that they had not eaten before. Researchers observed that an immunosuppresive cell, called a Treg cell, was produced in the gut. These Treg cells blocked the immune response to the new substances.

Fast facts about allergies
  • 15 million Americans have a food allergy
  • Food allergies affect 4% of adults
  • 8% of children are affected, especially younger children.

Learn more about allergies

It was not known if this would happen when young mammals encountered new foods in “real life.”

Surh used “antigen-free” mouse models to represent an immunological blank slate. The mice were raised in a germ-free environment. They were also fed a diet of amino acids, the building blocks of proteins, instead of foods that contain the proteins themselves.

This made the mice “immunologically naïve,” because amino acid building blocks are not big enough for the immune system to recognize them. It meant that the mice had little or no previous contact with antigenic proteins and other macromolecules.

Other mice were germ free but fed on a normal diet.

Molecular marker analysis revealed that the mice that consumed amino acids had no Tregs in the small intestine. In contrast, mice that were fed a normal protein diet had a large number of Tregs.

This suggests that when proteins are contained in food, they stimulate Treg development. It also indicates that Tregs in the gut of normal mice might serve to prevent a potentially disastrous immune response to those proteins.

The researchers also demonstrated that food and beneficial bacteria in the gut generate different types of Tregs.

Germ-free mice appear to have only food-dependent Tregs and lack the kind of Tregs that are induced by healthy microbes. These mice are also known to be very susceptible to allergies.

The scientists deduced that to prevent allergic symptoms, the gut needs both food- and microbe-induced Tregs.

Finally, the team wanted to find out what happens when immune cells fail to ignore harmless antigens.

They transferred “reporter” T cells into antigen-free mice and fed them a protein they had never encountered. The reporter T cells were designed to indicate an immune reaction.

The protein-fed mice experienced a massive immune reaction compared with the mice that were fed a normal diet. Surh calls this reaction the default response.

The reaction resembled the type of immunological storm caused by harmful microbes.

The conclusion was that this reaction happened because the antigen-free mice did not have a population of immunosuppressive Tregs ready that could have dampened an inflammatory response to food.

This could be why children, who are less exposed than adults to different types of food, are more prone to food allergies.

It also suggests people outgrow their allergy as they expand their range of Tregs that recognize new foods as “safe.”

The next step is to investigate the cellular and molecular details of how the “default” strong T cell response to food is regulated. The team plans to pay focus on specific items that are commonly related to allergies, such as peanuts, egg and so on.

Surh says:

“The immune system evolved to protect us from things that are not ourselves, like viruses or pathogens, yet we consume nutrients, which are themselves foreign. Our work shows food tolerance is acquired and involves specific populations of T cells that develop following its consumption. Without them, we would mount a strong immune response to macromolecules contained in food.”

Medical News Today has previously reported on research suggesting that breast feeding does not prevent allergies.