Immunosuppression by Hydatidiform Mole Trophoblast Is Neutralized by Monoclonal Antibodies to β‐Interferon

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Abstract
In sheep and cattle, trophoblast-derived interferons serve as signals for the maternal recognition of pregnancy and may regulate the immunologic relationship between the fetus and mother. In this study, soluble extracts prepared from human hydatidiform mole decidua (DE) and trophoblast (HME) were screened for immunosuppressive activity using an interleukin (IL)-2-dependent T-cell line (CTLL2). Antibody neutralization studies were performed with monoclonal antibodies to alpha- and beta-interferon (IFN). HME suppressed (P < 0.05) IL-2-stimulated (2 IU/well) CTLL2 proliferation at doses ranging from 500 (52 +/- 2% of control) to 100 (74 +/- 5%) micrograms/ml concentrations. DE also suppressed (P < or = 0.05) CTLL2 proliferation in a dose-related fashion from 500 (20 +/- 6% of control) to 100 (71 +/- 8%) micrograms/ml doses. Preincubation with the alpha- and beta-IFN antibody preparations had no effect on CTLL2 suppression by the DE sample. In contrast, the beta-IFN antibody partially neutralized the suppressive activity of HME at each of the dilutions tested. The monoclonal antibody to alpha-IFN failed to neutralize HME suppression at any of the doses tested. These results suggest that hydatidiform mole trophoblast produces a beta-IFN-like macromolecule that may abrogate maternal rejection responses that are harmful to the developing fetal allograft.