The influence of initial exposure timing to β-lactoglobulin on oral tolerance induction

Abstract

Background: Although a number of studies have investigated the induction of oral tolerance to several proteins, relatively little is known about the induction of oral tolerance to β-lactoglobulin, one of the major antigenic proteins in milk. Objective: We investigated the influence of the timing of the initial β-lactoglobulin exposure on oral tolerance induction and examined some characteristics of the tolerogenic immune response. Methods: BALB/c mice were given β-lactoglobulin prenatally or from the third or fifth postnatal week, bred for 17 weeks, and compared with unexposed control mice. Specific plasma anti-β-lactoglobulin antibodies (total IgG, IgG subclasses, IgM, and IgE), antigen-specific splenocyte responses, frequencies of antibody-producing cells, and cytokine production by splenocytes, intestinal mucosal lymphocytes, and Peyer’s patches were analyzed. Results: Differences were observed among the 4 groups of mice in changes of plasma anti-β-lactoglobulin antibody titers, antigen-specific T-cell proliferation, and frequencies of antibody-producing splenocytes, intestinal mucosal lymphocytes, and Peyer’s patch cells after the first exposure to β-lactoglobulin. The onset and duration of the immunologic responses were found to be dependent on the timing of antigen exposure. Prenatal exposure to antigen facilitated the induction of oral tolerance to β-lactoglobulin, whereas delayed antigen exposure retarded tolerance. The induction of oral tolerance was associated with increased IL-4 and/or IL-10 production and decreased IL-12 production. Conclusion: Our results suggest that the timing of initial antigen exposure greatly influences the induction of oral tolerance to β-lactoglobulin and that altered secretion of regulatory cytokines may be responsible for the differences in antibody production and oral tolerance induction. (J Allergy Clin Immunol 1999;104:870-8.)