Soluble factors produced by isolated first-trimester chorionic villi directly inhibit proliferation of T cells

Abstract

Supernatants from human trophoblast cultures have been reported to be both suppressive and stimulatory of mitogen-induced T-lymphocyte transformation. These discordant observations have been attributed to methodologic differences among laboratories, but may instead relate to inadvertant cellular contamination during long-term culture. Retrieval of chorionic villi for genetic analysis has provided an opportunity to evaluate the immunoregulatory activity of the isolated villus preparation, unencumbered by extended culture techniques. Primary cytotrophoblast cultures were established from karyotypically and clinically normal pregnancies and the supernatants were recovered. Allogenic mononuclear cells, stimulated by phytohemagglutinin, were uniformly inhibited by trophoblast supernatant (mean inhibition, 34.3%). This inhibition was verified in one-way, mixed lymphocyte cultures and suppression of T cells occurred in a dose-dependent fashion over a range of trophoblast supernatant concentrations. No evidence of suppressor T-cell induction by trophoblast supernatant was noted with the use of both phenotypic studies of lymphocytes incubated with trophoblast supernatant and a functional suppressor T-cell inducer assay. We believe that the immunoregulatory properties of trophoblast supernatants identified with the use of these methods more closely approximate the paracrine function of the in situ villus.