Accessory Cells Provide More Than One Signal for Lectin Mitogen-Stimulated Proliferation of Human Lymphocytes

A culture system was developed in which human peripheral blood mononuclear cells (PBMC) depleted of Ia-expressing cells did not proliferate in response to the lectin mitogen phytohemagglutinin (PHA). These cells were able to respond to mitogen if purified autologous accessory cells were added back to the culture, thus showing an absolute requirement for Ia-expressing accessory cells in mitogen-driven T-cell proliferation. The identity of these accessory cells was shown to be not only monocytes but also Ia-expressing B cells and possibly other unidentified Ia-bearing cell types. Human interleukin-1 (IL-1) in the lectin mitogen-unresponsive culture system was found unable to reconstitute normal human T-cell proliferation. This suggests that those cells with Ia surface antigen acting as accessory cells must deliver more than an IL-1 signal for T-cell proliferation. The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was tested for its ability to replace necessary Ia-expressing accessory cells. TPA was able to replace accessory cells in culture, thus mimicking the Ia-expressing accessory cells and all their delivered signals in the triggering of human lymphocytes.