Selective action of alkylating agents against cells participating in suppression of antibody responses

The effect of several alkylating agents on the induction and expression of specific suppressor cell activity induced by supraoptimal immunization (SOI) with (4 x 10(9) ) SRBC was studied. Splenocytes taken 8-28 days after SOI and transferred to normal syngeneic recipients together with optimal dose of (3 x 10(8) ) SRBC caused 70-90% suppression. By contrast splenocytes harvested 2 days after SOI did not exert a significant suppressive effect. Treatment of donor mice with 30 mg/kg BCNU, CCNU, or MeCCNU, 8 mg/kg Melphalan or as much as 200 mg/kg Cy 2 days before SOI uniformly had no effect on the subsequent development of suppressor cells. By contrast, different drugs had diverse effects when injected after SOI: both BCNU and Cy injected 2 days post SOI alleviated suppression, whereas CCNU, MeCCNU and Melphalan injected 2 days post SOI were without effect. Another diversity between BCNU and Cy was noticed when the administration of drugs was delayed further. While Cy alleviated suppression 12 days post SOI, BCNU was ineffective at this time. Dose response and time course studies revealed that the effect of Cy was most severe when injected 2 days post SOI and gradually diminished with the passage of time after SOI. These results have been discussed in the light of the current concepts of multiple cell participation in the induction and expression of suppressor cell function.