PRETREATMENT OF DONOR STIMULATOR CELLS BY 16,16 DIMETHYL PROSTAGLANDIN E-2 INFLUENCES THE RECIPIENT IMMUNE-RESPONSE

Background. Immunosuppressive strategies have largely ignored donor-de rived stimulatory cells as a target. This study examined whether lipop olysaccharide (LPS) or 16,16 dimethyl prostaglandin E-2 (dmPGE(2)) pre treatment of stimulator cells from B10.BR mice influences effector fun ction of responder T lymphocytes from C3H/HeJ mice in vitro or in vivo . Methods. B10.BR spleen cells were incubated in vitro in the presence or absence of dmPGE(2) or LPS before the cells were used as stimulato rs in a mixed lymphocyte culture (MLC) with T cells from C3H/HeJ mice. In parallel studies, B10.BR mice were treated in vivo with dmPGE(2) o r LPS; spleen cells from these animals were used as stimulators in an MLC and skin was harvested for shin grafts. Cells from untreated or pr etreated mice were examined for expression of intercellular adhesion m olecule-1 (ICAM-1), B7-1, and B7-2 by fluorescence-activated cell sort er analysis. ICAM-1 mRNA transcripts were determined by reverse transc riptase-polymerase chain reaction. Results. Stimulation of B10.BR-deri ved spleen cells with LPS before their use as stimulator cells in a ML C resulted in an increase in responder T-cell proliferation compared w ith use of unstimulated spleen cells (p < 0.05). lit contrast, pretrea tment of stimulator spleen cells with dmPGE(2) resulted in dose-depend ent inhibition of the responder T-cell proliferation, with maximum eff ect seen using a concentration of dmPGE(2) of 10(-5) mol/L. The decrea sed expression of interleukin-1, tumor necrosis factor, leukotriene B- 4, procoagulant activity and ICAM-1 by the dm PGE(2)-pretreated spleen cells correlated with their inefficiency in stimulating T-cell prolif eration. Spleen cells harvested from B10.BR mice previously injected w ith dmPGE(2) similarly were inefficient as stimulator cells. Skin graf t survival was delayed, but not prevented by in vivo pretreatment of d onor mice with dmPGE(2). Conclusions. These data demonstrate the effec t of immunomodulation of allogeneic stimulator spleen cells on subsequ ent responder T-lymphocyte function and allograft survival.