Human Placental Cells that Regulate Lymphocyte Function

Abstract

A B S T R A a . We examined normal human placenta for an immunologic function by measuring the release of soluble inhibitory factor (SIF). SIF is a product of normal T lymphocytes and of the JEG-3 choriocarcinoma cell line, and blocks proliferative and antibody-producing responses of mononuclear cells. SIF can be further characterized by a noncovalently linked subcomponent, lipid suppressor substance. The villous surfaces of six normal human placentae were digested with collagenase to obtain a population of predominantly multinucleated giant cells. These cells were maintained in standard culture for 5 days after which the cell-free conditioned culture medium was assayed for SIF content by measuring suppression of VH] thymidine incorporation into lymphocytes stimulated by low-dose phytohemagglutinin. Undiluted placental SIF induced 88% inhibition of this response (p < 0.001). The placental SIF was found to contain lipid suppressor substance, as does SIF from mononuclear cells. We determined this by thin-layer chromatography where a peak of suppressive activity occurred at Rf 0.32 (PHjthymidine incorporation reduced from 21810 + 308 to 4121 2 214 cpm); this is the position on thin-layer chromatography to which mononuclear cell lipid suppressor substance migrates. Ion exchange chromatography comparing the elution patterns of lymphocyte-SIF and placental-SIF indi: cated that both eluted in the fraction of 40-50 mM P W buffer, further suggesting identity between these two substances. SIF from placental and lymphocyte sources functioned by inducing the presence of suppressor cells in culture. Mononuclear cells were incubated for 48 h in SIF; the resultant cell population reduced [H3]thymidine incorporation into phytohemagglutinin-stimulated lymphocytes from 21170 + 1721 to 8612 2 311 cpm (60% inhibition, p < 0.001). Adherent cells were not required for function of these cells and they were not sensitive to mitomycin C. The placenta helps prevent immunologic rejection of the fetus by several mechanisms; it functions as a barrier, it is devoid of human histocompatibility leukocyte antigen markers and it has immunologic functions. The studies presented herein indicate that the placenta releases a substance that induces the formation of suppressor cells. These data support the hypothesis that placental cells have an immunoregulatory function. (Pediatr Res 23: 212-218, 1988) Abbreviations Ec, effector cells FCS, fetal calf serum PH]TdR, tritiated thymidine

The interleukin 2 gene is expressed in the syncytiotrophoblast of the human placenta.

“…Placentas or trophoblasts have been reported to produce a variety of immunoregulators. Soluble inhibitory factor (also a product of T lymphocytes) is released by the placenta (55). It has the ability to suppress lymphocyte proliferation and antibody synthesis.…”

Human nonspecific suppressive lymphokines

“…SIF has also been identified in normal human sera and found to be present at very high concentrations in serum from a patient with an unusual cutaneous lymphoma (57). SIF is also produced by cultures of multinucleated giant cells obtained from the villous surfaces of normal human placentae (58).…”