The effect of immunomodulation of stimulator antigen presenting cells on subsequent responder T-cell function

In this study, we examined whether lipopolysaccharide (LPS)-, interferon-gamma (IFN-gamma) or 16,16-dimethyl prostaglandin E2 (dmPGE2)-pretreatment of stimulator spleen cells from C57BL6 (B6) mice affects effector function of responder T-lymphocyte from C3H/HeJ mice. Stimulation of B6-derived splenic mononuclear cells (SMNCs) with LPS (10 micrograms/ml) prior to their utilization as stimulator cells in a mixed lymphocyte culture (MLC) resulted in an increase in responder T-lymphocyte proliferation compared to utilization of unstimulated SMNC (P < 0.05). IFN-gamma demonstrated similar effects in a dose dependent fashion with maximal stimulatory effect seen at 1000 U/ml. In contrast, pretreatment of stimulator SMNC with dmPGE2 resulted in dose-dependent inhibition of the responder T-lymphocyte proliferation with maximum inhibitory effect seen using a concentration of dmPGE2 of 10(-5) M. The presence of indomethacin in the MLC did not reverse this effect. These data demonstrate the effect of immunomodulation of stimulator spleen cells on subsequent T-lymphocyte function.