Induction of “Low Dose” Tolerance to a Bacterial Somatic Antigen in Neonatal Mice

Abstract

THE concept of “low dose” tolerance rests on the observation that specific immunological unresponsiveness can be induced by extremely small doses of antigen, sometimes in quantities too small to provoke antibody formation as such^1–3. The initial observations were made with soluble serum proteins, which are generally not considered “strong” antigens^4,5. Low dose tolerance can be induced also to the highly immunogenic protein antigen derived from Salmonella flagella, as assessed at the level of serum antibody^6,7. Furthermore, recent studies at the level of antibody forming cells indicate that immunological tolerance to complex antigens such as sheep erythrocytes and bacterial extracts, as well as to serum proteins or chemical haptens, can be induced in neonatal or adult animals^9–14. In this regard, relatively large doses of antigen are reportedly necessary to induce tolerance in adult rodents to a bacterial antigen such as Escherichia coli lipopolysaccharide (LPS). For example, 10–15 mg of the LPS is necessary to induce tolerance, as measured by an indirect haemolytic plaque assay with antigen coated sheep erythrocytes^15,16. Lower doses of LPS reportedly induce only immunity.