Of the 15 million Americans who have food allergies, the majority are children. One in every 13 kids in the United States currently has a food allergy but, fortunately, many will outgrow them.

Past research has shown that early exposure to allergenic foods can reduce children’s risk of developing food allergies, but has offered no explanation for why children are able to outgrow these allergies, or why they are more susceptible in the first place.

Dr. Charles Surh, a researcher for the La Jolla Institute for Allergy and Immunology (LJI), has now solved these mysteries in a new study, published in the online version of Science. The study relied upon a rarely used and once-forgotten research tool: antigen-free mice.

Antigens are responsible for telling the immune system that a foreign substance, including food, has entered the body. If those substances are not familiar to the body, the immune system deems them hazardous and attempts to fight them off.

For mice to be antigen-free, they are raised in a germ-free environment and are only fed amino acids — the building blocks of proteins — which are too small to be recognized by the immune system as antigens. Without having ever been exposed to antigens, these mice have a “blank slate” immune system that mimics those of infants and toddlers, who have not been exposed to most foods.

Prototypes of antigen-free mice were first developed over 30 years ago, when most nutrition research was still being conducted. "We brought them back because we're no longer in the dark ages,” Surh says. “We know a lot more about immunology! Decades ago, researchers could monitor changes in lymphocyte numbers but couldn't distinguish between cell types like we can now."

Surh’s decision to use antigen-free mice was based on the hypothesis that, over time, the immune system learns to tolerate food that was initially mistaken as hazardous – a hypothesis supported by the past research that suggested exposure to allergenic foods can prevent allergies.

Other prior research has established our bodies distinguish good antigens (safe foreign substances) from bad antigens (harmful pathogens) by using T-regulatory cells (Tregs). When novel foods were fed to regular mice, Tregs developed in the gut and blocked the body’s default immune response against those foods.

This research was monumental, but still left scientists uncertain of whether this process occurred in young mammals. By using antigen-free mice, however, Surh was able to confirm this suspicion. Compared to the antigen-free mice that had no Tregs in their small intestines, regular mice had a large amount, suggesting food proteins stimulate Treg development.

Additionally, Surh now believes that two distinct types of Tregs are required to prevent food allergies. During the study, the researchers identified that food and beneficial bacteria each generate their own unique type of Tregs, because germ-free mice only possessed food-dependent Tregs, and not Tregs induced by bacteria. Since germ-free mice are known to be highly susceptible to allergies, Surh hypothesizes that the presence of both food- and microbe-induced populations of Tregs is required to prevent food allergies.

"Our work shows food tolerance is acquired and involves specific populations of T cells that develop following its consumption,” Surh says. “Without them, we would mount a strong immune response to macromolecules contained in food."

Overall, the research suggests that children are more susceptible to food allergies, simply because they have been exposed to fewer foods. And once they are exposed to more, the body becomes familiar with those antigens and an allergic reaction is avoided.