Suppression of reaginic antibody formation. I. Induction of hapten-specific tolerance.

Reaginic antibodies to DNP and ovalbumin were indcued readily in B6D2F1 mice by a single intraperitoneal injection of 1 mug of DNP-ovalbumin suspended with 1 mg aluminum hydroxide in 0.5 ml of saline. The formation of anti-DNP reaginic antibody was completely suppressed by treatment of mice with a conjugate consisting of the hapten coupled to an isolgous nonimmunogenic carrier, viz., murine phi-globulins. However, this treatment did not affect the level of antibody formation to the carrier of the immunizing antigen. The induction of unresponsiveness was dose dependent, complete suppression being achieved with 1 mg of the tolerogen. The state of unresponsiveness could be maintained for prolonged periods (these observations were made over a period of at least 8 months) by repeated injections of the tolerogen at intervals of 2 months. More importantly, the state of unresponsiveness could be induced readily not only in normal, but also in sensitized mice, i.e., this treatment was capable of abrogating an ongoing reaginic response, and the suppression was immunologically specific. Hence this system appears to have a great potential for adaptation to the treatment of allergic diseases in man.