Immunological unresponsiveness in rabbits produced by neonatal injection of defined antigens

The phenomenon of immunological unresponsiveness induced in the neonatal rabbit by a single injection of a defined protein antigen, has been characterized semiquantitatively, and studies bearing upon the mechanism of such unresponsiveness have been presented. A single intraperitoneal injection at birth of 10 to 100 mg. BSA, HGG, ovalbumin, or a human macroglobulin, or an oral feeding of 100 mg. BSA, induced a state of unresponsiveness lasting at least 90 to 120 days. 100 mg. BSA given from birth to 17 days of age, but not later, produced unresponsiveness of 90 to 120 days' duration. Data are presented which show that the duration of unresponsiveness is finite and related to the amount of antigen given at birth, and that it may be indefinitely prolonged by repeated injections of antigen. Disappearance of injected antigen in the unresponsive animal was exponential with time, with no accelerated or immune phase. Administration of the antigen in adjuvants resulted in significant shortening of the duration of unresponsiveness. The transfer of immune cells to the unresponsive host while resulting in vicarious antibody formation, did not affect the underlying unresponsive state. Negative results of attempts to produce unresponsiveness to a variety of bacterial antigens are presented. The implications of the data are discussed, particularly in reference to the other experimental models of immunological tolerance, and to the various theories of acquired immunity. It is clear that any satisfactory theoretical explanation of acquired immunity will have to account simultaneously for the phenomena of immune tolerance.