Phorbol ester replacement of helper cell and interleukin 2 requirements in gamma interferon production.

Immune interferon (IFN-gamma) production by mitogen-stimulated C57BL/6 mouse spleen cells required both Lyt 1+,2- and Lyt 1-,2+ lymphocytes. The Lyt 1-,2+ cells were the IFN-gamma producers, whereas the Lyt 1+,2- cells were the helpers. Interleukin 2 mediated the Lyt 1+,2- cell help. Phorbol myristic acetate (10 ng/ml) completely replaced Lyt 1+,2- helper cell or interleukin 2 requirements in IFN-gamma production. The phorbol ester exerted its helper effects by direct interaction with IFN-gamma-producing Lyt 1-,2+ cells and not through stimulation of production of interleukin 2 by Lyt 1+, 2- cells. Suppressor cell effects in IFN-gamma production were also completely abrogated by phorbol myristic acetate. The data suggest a mechanism for phorbol myristic acetate regulation of IFN-gamma production at the cellular level.