RESISTANCE OF T SUPPRESSOR CELLS TO CYCLOPHOSPHAMIDE ADMINISTRATION IN TOTAL-LYMPHOID-IRRADIATED MICE

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Abstract
The effect of administration of cyclophosphamide (Cy) on the susceptibility of mice to tolerance induction and its influence on the rate of induced T suppressor cells in antigen-specific and nonspecific systems was assessed using mice that had undergone total lymphoid irradiation (TLI). Tolerance to bovine serum albumin (BSA) was induced in adult mice conditioned by a short course of fractionated total lymphoid irradiation with an injection of nondeaggregated BSA; Cy was administered upon termination of TLI, 2 days before administration of the tolerizing antigen. Susceptibility to tolerance induction and rate of induced T suppressor cells were assessed 1 mo. later. Cy-treated TLI mice and mice treated with TLI alone did not respond to a challenge with DNP[dinitrophenylated]-BSA in complete Freund''s adjuvant; a good response was obtained to an unrelated protein antigen. The induced T suppressor cell rate was measured by inhibition of a secondary anti DNP-BSA response in an adoptive transfer system. The rate of non-antigen-specific T suppressor cells was measured by inhibition of the mixed leukocyte reaction with Concanavalin A-induced T suppressor cells obtained from spleen cells of TLI-treated, or Cu-treated mice, or those given both treatments. Evidently, Cy treatment of TLI-conditioned mice does not reduce the rate of induced T suppressor cells in antigen-specific and antigen-nonspecific systems.