Preventive effect of a synthetic immunomodulator, 2-carboxyethylgermantum sesquioxide, on the generation of suppressor macrophages in mice immunized with allogeneic lymphocytes

The effect of 2-carboxyethylgermanium sesquioxide (Ge-132) on the generation of splenic suppressor macrophages (S-MØ in C3H/He mice (H-2^k) immunized with allogeneic spleen cells from C57B1/6 mice (H-2^b) was investigated. We have previously demonstrated that S-MØ expressing I-J antigen, which appeared during alloimmunization, inhibited cytotoxic T lymphocyte (CTL) generation in the MLR and the elimination of these S-MØ before subjection to the MLR resulted in more effective generation of CTL. The CTL activity, which was determined in vivo by the Winn's test, was markedly enhanced when immunized mice received a 100 mg/kg dose of Ge-132. The compound was found to be the most efficacious when injected simultaneously with the immunization. The activity of allospecific CTL co-cultured with MØ fractions obtained from immunized mice in a 4-h ⁵¹Cr-release assay was shown to be 31% lysis of the target cells as compared with 90% lysis of the target cells in effector cells co-cultured with normal MØ fractions. In contrast, effector cells co-cultured with MØ fractions from Ge-132-treated immunized mice lysed 95% of the target cells. Analysis of the level of I-J antigen expression on macrophages (MØ obtained from mice 7 days after immunization revealed a > 2.5-fold increase, whereas I-A antigen expression remained constant when compared with splenic MØ from naive mice. In contrast, the opposite effect on I-J and I-A antigen expression was observed in splenic MØ from alloimmunized mice treated with Ge-132. These results suggest that Ge-132 could regulate CTL generation in alloimmunized mice by preventing the generation of I-J⁺ S-MØ Ge-132: 2-carboxyethylgermanium sesquioxide