Tumour necrosis factor alpha binding to human and mouse trophoblast.

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with pleiotropic effects, modulating cell growth, differentiation, and synthesis of various substances. Recent demonstration of TNF-alpha mRNA and protein in the uteroplacental unit suggests that this cytokine may be involved in the development of the embryo. To determine whether the embryo itself binds TNF-alpha, mouse blastocyst outgrowths and human first trimester villous trophoblast were analysed for TNF-alpha binding. Our experiments revealed that binding of TNF-alpha could be specifically detected on the trophectoderm of the outgrowing mouse embryos. They also show a complete disappearance of the colony-stimulating factor 1 (CSF-1) receptor that occurs shortly after the binding of TNF-alpha by the trophectoderm. In human first trimester villous trophoblast, TNF-alpha binding was found to be predominantly detectable on the syncytiotrophoblast and to a lesser extent on the cytotrophoblastic cells. Binding was not observed on adjacent embryonic or maternal cells. Our results further support the idea that TNF-alpha as well as other cytokines may modulate early embryonic development and implantation.

Production of colony-stimulating factor 1 by T cells: possible involvement in their interaction with antigen-presenting cells.

Colony-stimulating factor 1 (CSF-1) is required for the growth and differentiation of mononuclear phagocytes, and is also involved in modulating various activities in mature cells. We report herein that T-cell lines produce 4.6 and 1.5 kb mRNA species of CSF-1, and express the CSF-1 protein on their outer membranes, as determined by immunofluorescence staining with anti-CSF-1 antibodies. The CSF-1 protein is biologically active. Interested by the possible immunoregulatory function of CSF-1, we assessed its effect in an assay of antigen presentation to the T cell lines. We found that anti-CSF-1 antibodies inhibited T-cell stimulation. Moreover, soluble CSF-1 could not overcome this inhibition, but exerted a significant inhibitory activity on the interaction between T cells and antigen-presenting cells leading to T-cell activation and proliferation in vitro. Based on these observations we propose that T-cell CSF-1 may be involved in the interaction of these cells with CSF-1 receptor bearing antigen-presenting cells.

Cytokines modulate preimplantation development and pregnancy.

Using two different models of pregnancy failure in mice, we show in this communication that preimplantation embryonic development can be controlled, in vivo, with cytokines. In one model, described by us previously, CSF-1 is shown to block gestations in plugged females due to its induction of defective early development. Pregnancies and preimplantation development are shown here to be restored to normal by TNF alpha or GM-CSF but not by TGF beta 1. In the second model, we reveal that CBA/J females plugged by various male strains produce spontaneously an extremely high proportion of abnormal precompaction embryos. Normal morulae and blastocysts, able to further develop and implant in vitro, are shown here to be induced by TNF alpha and to a lesser extent by GM-CSF and IL-1 alpha. These results suggest strongly that cytokines are potent modulators of early development. They may provide new and interesting insights into early events of mammalian embryonic development.