Differential expression of migration inhibitory and migration stimulatory factors in two lines of mice genetically selected for high or low responsiveness to phytohemagglutinin. 2. Effects of mitogenic or allogeneic stimulation.

Expression of migration inhibition factor (MIF) following in vitro stimulation with phytohemagglutinin (PHA) or allogeneic cells was explored in two lines of mice genetically selected for the high (Hi/PHA) or low (Lo/PHA) response of their lymphoid cells to PHA. Hi/PHA mice also have greater cell-mediated immune responses in mixed lymphocyte culture and graft-versus-host reactions, the poorer cell-mediated immune response of Lo/PHA being accompanied by a higher frequency of malignant tumours. Expression of MIF in PHA-pulsed spleen cell supernatants measured by a sensitive photoelectric method was found to be modulated by the concomitant presence of migration stimulation factor (MStF) derived from T cells. Both lymphokines were better expressed in Lo/PHA, as compared to Hi/PHA, under appropriate experimental conditions. Use of a low proliferative dose of mitogen (5 micrograms/ml PHA, 2-hour pulse) followed by culture in serum-free medium led Lo/PHA to express the highest titres of MIF, whereas a proliferative dose of PHA (50 micrograms/ml, 2-hour pulse) caused abrogation or occultation of expression of MIF and elective expression of MStF in this line. Hi/PHA mice expressed MIF equally at both mitogen doses, with transient expression of MStF followed by MIF after 50 micrograms/ml PHA, the kinetics of expression of the two lymphokines being different. Expression of MStF by spleen cells was an early event after PHA stimulation. In contrast to mitogenic stimulation, allogeneic stimulation in one-way mixed lymphocyte culture led to similar expression of MIF by both lines of mice. The implications of these findings are discussed.