Effect of immunosuppressive drugs on T and B lymphocytes in guinea pigs.

Changes in the number of T and B lymphocytes were assessed in guinea pigs following administration of immunosuppressive drugs. I cells were measured by rosetting with papainized rabbit erythrocytes, B cells by complement rosettes. After a single intraperitoneal dose of cyclophosphamide (150 mg/kg), the number of T and B cells in both peripheral blood and lymph node suspensions decreased by 60%-70%. The reduction of both elements persisted through day 5 after drug administration. There was a differential rate of recovery; T cells were restored by day 8; B cells remained subnormal until day 14. Chlorambucil (10 mg/kg) produced less striking changes in the number of both types of lymphocytes; the reductions ranged from 25%-35%. Neither 6-mercaptopurine (100 mg/kg) nor methotrexate (75 mg/kg) altered the number of either cell type in the blood or lymph node samples. Hydrocortisone acetate (400 mg/kg) reduced lymph node T and B cells within 2 days of administration; blood values did not decrease until day 5. Additional studies indicated that five consecutive doses of cyclophosphamide (20 mg/kg/day) and chlorambucil (1 mg/kg/day) caused both T and B lymphopenia; none of the other drugs significantly depleted blood lymphocytes. These results suggest that the initial effects of cytotoxic agents and hydrocortisone are relatively nonselective in terms of changes in functional classes of lymphocytes. The cell-cycle specificity of cytotoxic drugs, rather than a specific toxicity for a particular class of lymphocytes, appears to be the prime determinant in the killing of immunologically competent cells.