Immunosuppressive Drugs Combined With Heterologous Antilymphocyte Serum for Allograft Prolongation

The administration of a single injection of rabbit antimouse lymphocyte serum (ALS) results in a temporary lymphopenia and the prolonged survival of A strain skin grafts on CBA mice. Both lymphopenia and immunosuppression can be prolonged by the addition of a combination of a purine and a pyrimidine antagonist (bromo-deoxyuridine and thioguanine) without further ALS administration. The optimal dose of drugs required for maximal immunosuppression and minimal toxicity can be monitored continuously during administration by maintaining a peripheral lymphocyte count between 500 and 2000/mm3. Greater degrees of immunosuppression can be attained by the addition of nontoxic doses of cortisone acetate to the single ALS injection. These studies suggest that the dangers of the prolonged administration of heterologous serum products may be avoided by the addition of standard immunosuppressants to short courses of antilymphocyte sera.