Interleukin-12- and interleukin-2-stimulated release of interferon- gamma by uterine CD56++ large granular lymphocytes is amplified by decidual macrophages

Abstract

Numerous studies have suggested that interferon-gamma (IFN-gamma) exhibits an inhibitory effect on conceptus development during pregnancy, and recent investigations have shown that decidual CD56++, CD16- large granular lymphocytes (LGL) contain mRNA for IFN-gamma. We have investigated the influence of exogenous interleukin-12 (IL-12) and interleukin-2 (IL-2) on IFN-gamma secretion by cultivated LGL and macrophages isolated from first trimester human decidua. The effect of decidual macrophages on IFN-gamma secretion by LGL was also assessed using co-incubation experiments. Neither IL-12 nor IL-2 stimulated the secretion of IFN-gamma by decidual macrophages. IL-12 alone, but not IL-2 alone, stimulated the release of IFN-gamma by LGL. However, IL-2 acted synergistically with IL-12 to enhance the release of IFN-gamma by LGL. Unstimulated and IL-12- and IL-2-stimulated LGL incubated with macrophages exhibited a marked increase in secretion of IFN-gamma compared to those in monoculture. This effect was also seen when the LGL and macrophages were separated by a semi-permeable membrane. The results suggest that interactions between decidual LGL and macrophages, possibly mediated by soluble factors, could play a role in regulating IFN-gamma secretion at the materno-fetal interface and thus contribute to the control of invasion by the trophoblast.