Hydatidiform mole pregnancy trophoblast extracts differentially suppress interleukin-2-induced proliferation of human...

Immunoregulatory factors of trophoblast origin may partially abrogate maternal immune responses to the fetus during pregnancy. We have previously shown that soluble factors extracted from hydatidiform mole trophoblast suppress interleukin-2 (IL-2)-dependent proliferation of a cloned murine cytotoxic T cell line (CTLL-2). To characterize human T cell responses to this trophoblast extract, we measured the effects of molar tissue extracts (HME) on IL-2-stimulated proliferation of human T-lymphocytes and mitogen (PHA) transformed T-cell blasts (PHA-blasts). HME significantly (P less than 0.05) suppressed T-lymphocyte proliferation in response to 5 and 10 units/ml of IL-2 at 500 and 250 micrograms/ml, while no effect was observed at the 100 micrograms/ml concentration. Suppression by HME of IL-2-stimulated T-cell proliferation was partially overcome by the addition of excess IL-2. HME also suppressed (P less than 0.05) IL-2-stimulated proliferation of PHA-blasts at 500 and 250 micrograms/well at both 5 and 10 units/ml of IL-2. As observed with resting T-cell responses, no suppression of PHA-blast proliferation was observed using 100 micrograms/ml of HME. In contrast to the response of the resting T-cells to excess IL-2, HME suppression of IL-2-stimulated blast proliferation was not affected by increasing the concentration of IL-2. These results indicate that extracts from hydatidiform mole trophoblast contain immunosuppressive factors that block human T-cell clonal expansion by inhibiting the utilization and/or production of IL-2. Furthermore, the effects of HME are not reversed by excess IL-2 when PHA-blasts are reacted compared to resting T-cell responses, which are partially reversed in the presence of excess IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)