Drug-Induced Tolerance to Allografts in Mice

Mechanisms and kinetics of tolerance in AKR mice induced using i.v. priming with viable C57BL/6 spleen cells and treatment with cyclophosphamide 2 days later were analyzed. In this tolerance induction system, some lymphocyte populations mediating delayed foot-pad reaction and cytotoxic activity were resistant to tolerance induction and remained in a sensitized state after cyclophosphamide treatment. These populations were considered to be qualitatively distinct from populations sensitive to cyclophosphamide, because delayed foot-pad reaction and cytotoxic lymphocyte activity were stronger in tolerant mice than in control mice in the early stages of tolerance induction, but were not augmented after immunization with C57BL/6 spleen cells, C57BL/6 skin grafts, or EL4 tumor grafts in the absence of suppressor T cells. One of the important differences in these two lymphocyte populations may be the capacity for clonal expansion.