IMMUNOSUPPRESSION BY HYDATIDIFORM MOLE TROPHOBLAST IS NEUTRALIZED BY MONOCLONAL-ANTIBODIES TO INTERFERON-BETA

PROBLEM: 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. METHOD: 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). RESULTS: 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%) mu g/ml concentrations. DE also suppressed (P less than or equal to 0.05) CTLL2 proliferation in a dose-related fashion from 500 (20 +/- 6% of control) to 100 (71 +/- 8%) mu g/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. CONCLUSIONS: 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.