The absence of gut flora, the doses of antigen ingested and aging affect the long-term peripheral tolerance induced by ovalbumin feeding in mice

Several factors have been shown to affect the induction of peripheral tolerance induced by the oral route, also called oral tolerance. In the present study, we explored factors that shorten the duration of the IgG and IgE antibody unresponsiveness induced after ingestion of ovalbumin (OVA). Accordingly, we explored the effects of aging, the absence of gut flora, and ingestion of either one dose of 20 mg OVA or 5 doses of 1 mg OVA in young adult conventional (CV) mice and germ-free (GF) mice, and older CV mice. In young CV mice fed 20 mg OVA, IgG and IgE antibody unresponsiveness were still observed 2 to 3 months after feeding. In CV mice, neither aging nor 5 low doses of OVA prevented the induction of IgG and IgE antibody unresponsiveness but they reduced its duration. In young GF mice given 20 mg OVA, IgG antibody unresponsiveness only lasted between 7 and 21 days after feeding, but IgE antibody unresponsiveness lasted much longer. We believe these findings should be taken into account in the treatment of autoimmune and allergic diseases, for cases requiring conditions of antigen ingestion suitable for lasting suppression of peripheral antibody responses. The animal models used here might be of interest for better understanding of the mechanisms involved in the long-term persistence of oral tolerance.