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The Role of Antigen Dosage in Drug-Induced Immunologic Tolerance¹

From the Tufts University School of Medicine and the Blood Research Laboratory, Pratt Clinic-New England Center Hospital, Boston, Massachusetts

Abstract

The effect of varying the dosage of antigen (bovine serum albumin (BSA)) on the induction of immunologic tolerance in adult rabbits by the administration of a constant amount (10 mg/kg) of 6-mercaptopurine (6-MP) was studied. The doses of BSA employed ranged from 0.066 mg/kg to 66.0 mg/kg. Tolerance was not regularly achieved at doses of BSA below 66.0 mg/kg. The specificity of the tolerant state was demonstrated by normal responses to BGG, which was administered after the cessation of 6-MP treatment. It is proposed that the induction of immunologic tolerance by 6-MP is due to a state of relative antigen excess brought about by the administration of antigen to an animal whose lymphoid system has been depleted by the cytotoxic drug. The states defined as immunologic tolerance induced in young animals, immunologic paralysis and immunologic unresponsiveness may all depend on an increase in antigen relative to the number of available antibody-forming cells.

Footnotes

¹ Aided by USPHS Grants E-3091 (C1) and H-5373, and Atomic Energy Commission Grant AT (30-1)2032.