Mechanism of suppression of footpad reaction in mice by 12-tetradecanoylphorbol 13-acetate and 7,12-dimethylbenz[a]anthracene.

Abstract

We reported previously that footpad reaction (FPR) of BALB/c mice against sheep red blood cells (SRBC) was suppressed by the percutaneal administration of 12-tetradecanoyl 13-acetate (TPA), a tumor promoter, following that of 7,12-dimethylbenz[a]anthracene (DMBA), a tumor initiator. This effect could be transferred with Thy-1(+) and Lyt-2(+) spleen cells. These findings suggested that this effect was caused by induction of the antigen nonspecific T-suppressor cells and that the process of the induction consisted of two steps. In the present report, we studied the cells related to the first step of this process. The spleen cells from the donor mice on which 400 nmol of DMBA was painted were transferred to the recipient mice which had been immunized 1 hr before the transfer. Then, 8 nmol of TPA was painted on the recipient mice every day for a week. Nine days after the transfer, FR against SRBC was measured. FPR in the recipient mice was suppressed compared to the control, showing that the effect of DMBA can be transferred with the spleen cells. The results of the treatment of the cells to be transferred with monoclonal antibodies and complement show that the cells which is responsible for the transfer of the effect are Mac-1(+), Thy-1(-), Lyt-2(-) and Ia(-). Also the effect of DMBA could be transferred with peritoneal macrophages from the donor mice on which DMBA was painted and anti Ia antibody treatment of the macrophages did not abrogate the effect of transfer.(ABSTRACT TRUNCATED AT 250 WORDS)