Orally induced tolerance to casein in mice on normal mouse chow

We examined the ability of bovine casein to induce oral tolerance in BDF₁ mice raised on a normal mouse chow diet. Giving 20 mg casein 1 × or 4 × by intragastric tube or for 28 days at 1 mg/ml in drinking water failed to have a significant effect (P > 0.2) on the subsequent immune response to parenteral casein, suggesting that casein was not an effective oral tolerogen. However, we discovered that most normal mouse chow contains casein. When BDF₁ mice were raised on a casein-free diet, and treated as above, they showed marked suppression of subsequent responses to parenteral casein (P < 0.01). Our results indicated that mice on the normal diet were presuppressed by the dietary exposure. Examination of several other normal mouse chows revealed that they all contained casein as a protein source. A possible effect of prior exposure must be considered in all experimental animal studies involving immune responses to antigens which may be present in the environment.