Lymphocytes in Peyer's patches regulate clinical tolerance in a murine model of food allergy

Abstract

Rationale Food allergy can elicit severe, potentially life-threatening anaphylactic reactions. In order to generate efficient strategies for an active cure of the disease, a better understanding of the pathogenic mechanisms of the disease is strongly needed. We investigated mechanisms of food allergy and tolerance to β-lactoglobulin (BLG) in gut-associated lymphoid structures. Methods β-lactoglobulin-specific IgG1, IgG2a, and IgE in serum from mice anaphylactic to BLG were analyzed by ELISA, and compared to those obtained in mice actively tolerized to BLG. The number of antibody secreting cells in the spleen and in Peyer's patches was determined by ELISPOT. Cell cytokine production after antigen-specific activation was measured by the same method. Further, mesenteric lymph node cells and Peyer's patch cells were transferred to naive mice and antibody production as well as antibody producing cell numbers were measured. Results We found that food-induced anaphylaxis or tolerance to BLG correlated with a specific antibody and cytokine pattern. IgG1 and IgE antibody titers, as well as IL-4 producing cell numbers were strongly increased in anaphylactic mice. IL-10 was found specifically in Peyer's patches cells from tolerant mice. Peyer's patch cells did weakly proliferate in anaphylactic mice after antigen activation, and activation was partially inhibited by tolerization. Furthermore, no Ab production was seen after adoptive transfer of Peyer's patches cells in naïve mice. Conclusions Our data show a specific role for lymphocytes in Peyer's patches for modulation of tolerance to BLG. A low IL-10 production in Peyer's patches might favor symptoms of food allergy.