Effect of fractional cyclophosphamide dosage on sheep red blood cell-delayed-type hypersensitivity response in mice

The CY-enhancing effect on DTH response of mice against SRBC was studied by administering to sensitized animals graded amounts of drug at various times during the immune response. The use of a staggered schedule for CY administration made it clear that this enhancing effect could be augmented even further by lowering the standard 200 mg/kg CY dose. Animals immunized on day 0 with 1 X 10(8) SRBC receiving 50 mg/kg doses on days -1, +1, and +4 showed higher DTH responses on day +7 than those similarly sensitized 1 day after the administration of 200 mg/kg body weight. In addition, we wanted to demonstrate that the TDTH effector cell is sensitive to CY in vivo, because a single 50 mg/kg dose inoculated on day +6 can lower by 50% an already established DTH response. This effect was not due to an effect of CY treatment on bone marrow-derived cells recruited to DTH responses; inhibition of DTH responses were transferred with spleen cells of CY-treated recipients. The action of CY is not dose-dependent; the administration on day +6 of a single dose of 200 mg/kg results in no further depression of the DTH reaction. We conclude that CY affects not only T supp cells, but also cell type(s) involved in the cell-mediated response of mice against SRBC, and that the DTH-enhancing effect of the drug is a blend of its action upon all these cells.