Phorbol ester tumor promoter modulation of alloantigen-specific T lymphocyte responses

The phorbol diester tumor promoter PMA was studied for its effects on T lymphocyte activation in allogeneic human mixed lymphocyte cultures. Lymphocyte proliferation was significantly enhanced in cultures with PMA at concentrations greater than or equal to 12.5 ng/ml, and interferon-gamma production was synergistically increased in cultures with PMA at concentrations greater than or equal to 5 ng/ml. In contrast, the generation of HLA-specific cytotoxic T lymphocyte activity was completely inhibited in cultures with PMA at concentrations greater than or equal to 5 ng/ml. Fluorescence-activated cell sorter analysis with OKT mouse monoclonal antibodies indicated these PMA effects on lymphocyte activation are associated with an increase in the number of activated OKT4-positive T lymphocytes.