Cellular Induction Mechanism of CD8+Suppressor T Cells by DMBA and TPA: Formation of CD4+Suppressor–Inducer T Cells

We investigated the cellular induction mechanism of antigen-nonspecific CD8+T suppressor cells which suppressed delayed-type hypersensitivity to sheep red blood cells, by treating BALB/c mice with 7,12-dimethylbenz[a]anthracene (DMBA), a tumor initiator, and 12-O-tetradecanoylphorbol 13-acetate (TPA), a tumor promoter. Macrophages were activated by painting with 400 nmol of DMBA on mice. And the macrophages plus TPA induced CD4+T suppressor inducer cells in the mice spleens. These cells were efficient at inducing CD8+T suppressor–effector cells. When 8 nmol of TPA was painted daily on mice for 3 days following the treatment with 400 nmol of DMBA, or when spleen cells from mice pretreated with 400 nmol of DMBA were cultured in 32 nmol/5 ml of TPA for 3 days, inducer cells were formed in the spleen. Both T suppressor–inducer cells and macrophages from mice treated with DMBA were shown to act with the formation of soluble factors, which may be different from IL-10.