Implication of Prostaglandin E2 in Soluble Factor-Mediated Immune Suppression by Murine Decidual Cells

ABSTRACT: Cells from the uteri of pregnant mice mediate profound nonantigen-specific and nonmajor histocompatibility complex-restricted immune suppression in vitro. In part, those cells accomplish suppression by releasing soluble suppressor factors. The purpose of the present study was to initiate identification of uterine cell suppressor factors. Immune suppression was assayed by the effect of decidual cells or in vitro generated supernatants of decidual cells on mixed lymphocyte reactions (MLR). The following findings support the designation of prostaglandin E₂ (PGE₂) as a primary suppressor molecule originating with decidual cells: (1) Suppression mediated by supernatants of decidual cells was relieved by removal of lipids but not proteins; (2) indomethacin, an inhibitor of prostaglandin synthesis, produced partial relief of suppression mediated by uterine cells and totally inhibited soluble suppressor factor generation by those cells; (3) decidual cells produced high levels of both PGE₂ and PGF_2a; (4) the addition of exogenous PGE₂ at levels comparable to those found in the decidual cell supernatants restored suppression by decidual cells and their supernatants whereas the addition of PGF_2a had no effect; (5) inhibition of the lipoxygenase pathway of arachidonate metabolism had no effect on cell or supernatant mediated suppression; (6) nonspecific suppressor mechanisms, such as arginine depletion and peroxide generation, were excluded as possible mediators of MLR suppression by decidual cells and their supernatants. Fractionation of decidual cells revealed at least three indomethacin-sensitive cell types: small, lymphocytelike cells, macrophages, and a third population of large decidual cells that was not identified by specific markers. The data strongly suggest that prostaglandins, primarily PGE₂, are involved in immunosuppression by cells from the uteri of pregnant mice.