TPA, tumor promoter-induced suppression of immunoglobulin secretion in human blood lymphocytes.
12-O-Tetradecanoylphorbol-13-acetate (TPA) modulates DNA synthesis and differentiation of normal and malignant human lymphoid cells. Using the reverse plaque forming assay and radioimmunoassay, we showed that nontoxic concentrations of TPA (5 to 10 ng/ml) inhibited Ig secretion of peripheral blood lymphocytes. This inhibition was dependent on T lymphocytes and not monocytes; TPA treatment of the B cell-enriched fraction slightly enhanced Ig secretion. Suppression was evident when the proportion of TPA-pretreated T lymphocytes exceeded 50%. TPA-induced suppressor cells were present in both OKT8+ (suppressor/cytotoxic) and OKT4+ ("helper/inducer") subpopulations. The suppression was diminished but not abolished by the irradiation of T lymphocytes. In addition, TPA treatment modulated the expression of OKT4 antigen, whereas the expression of OKT8, 9.6 (sheep erythrocyte receptors) and surface Ig remained unchanged. Modulation of OKT4 was energy dependent and was not blocked by a maximal saturation of TPA receptors at 4 degrees C. We postulate that TPA-induced suppression of Ig secretion is T cell dependent and is likely to be associated with proliferation and activation of OKT8+ and OKT4+ lymphocytes and the induction of OKT4+ suppressor cells.
D000328:Adult; D000921:Antibody-Producing Cells / Q000032:analysis / Q000187:drug effects* / Q000528:radiation effects; D000954:Antigens, Surface / Q000032:analysis; D002273:Carcinogens / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis* / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008875:Middle Aged; D010704:Phorbols / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000954:Antigens, Surface; D002273:Carcinogens; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate