The Production of Tolerance to Human Erythrocytes in the Rat with Cytosine Arabinoside or Cyclophosphamide

Selective immunologic tolerance to human O, Rh positive, erythrocytes was produced in Sprague-Dawley rats with cytosine arabinoside or cyclophosphamide. One method consisted of administering a suppressive course of drug and a high dose of antigen (1.7 × 1010 cells) after which intraperitoneal injections of antigen (1.7 × 109 cells) were given every 5 days. Alternatively, complete and long-lasting tolerance may be induced simply by suppressing the immune response to the high dose of the antigen three times at monthly intervals. Repeated stimulation in the presence of profound inhibition of DNA synthesis may have eliminated the specific clones capable of responding to the antigen, including memory cells provoked into DNA synthesis. Besides measurement of serum hemagglutinins, tolerance was confirmed by examining individual spleen cells using the immunocytoadherence (ICA) method. Specificity of the unresponsiveness was demonstrated by a normal response to sheep red blood cells. Tolerance to a strong cellular antigen can thus be achieved regularly with an antimetabolite or an alkylating agent.