Role of monocytes, alloantigens, and individual reactivity in the response of human lymphocytes to mitogenic factor.

The activity of mitogenic factors generated in human mixed lymphocyte cultures (MLC-MF) was analyzed with unstimulated mononuclear leukocytes used as responder cells. Unseparated or adherent, but not nonadherent, irradiated, autologous mononuclear leukocytes were found to significantly enhance the mitogenic activity of MLC-MF. The effect of MLC-MF was not inhibited by hydrocortisone at concentrations that inhibited MLC-MF production, indicating that the MLC-MF effect is direct and is not mediated through further production of mitogenic factors. Experiments in which MLC-MF was produced in a MLC between a HLA-D homozygous individual and her child suggested that soluble alloantigens do not play a role in the MLC-MF effect. Studies in one individual with MLC responses higher than other individuals indicated average MLC-MF production but above average response to MLC-MF. We conclude that MLC-MF is directly mitogenic for unstimulated lymphocytes, without requiring the simultaneously presence of either mitogen or antigen. In addition, the proliferative MLC reaction of antigen. In addition, the proliferative MLC reaction of individuals with strong responses to MLC-MF may be influenced significantly by the nonspecific clones recruited by MLC-MF.