Stimulation by food proteins plays a critical role in the maturation of the immune system.

The majority of contacts with foreign antigenic materials occur on the gut mucosa, and are represented by food proteins and the autochthonous microbiota. In the present study, we replaced intact dietary proteins by equivalent amounts of amino acids from weaning on and investigated its effects on the development of the immune system of mice. Adult animals reared on a balanced protein-free diet (Aa-mice) have a poorly developed gut-associated lymphoid tissue resembling suckling mice. They also display low numbers of lamina propria cells and TCRalphabeta intraepithelial lymphocytes, and low levels of secretory IgA. Levels of circulating IgG and IgA are also reduced in Aa-mice, whereas IgM levels are normal. In vitro cytokine production by cells from several lymphoid organs shows a predominant T(h)2 profile with a high concentration of IL-10 and IL-4, and a low concentration of IFN-gamma. These parameters also resemble the immunological patterns observed in pre-weaned mice. Thus, our data clearly show that exposure to food proteins after weaning has a physiological role in the maturation of the immune system both locally and systemically.