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Hydatidiform Mole Pregnancy Trophoblast Extracts Differentially Suppress lnterleukin‐2‐lnduced Proliferation of Human T‐Lymphocytes and PHA‐Blasts

ABSTRACT: 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<0.05) suppressed T‐lymphocyte proliferation in response to 5 and 10 units/ml of IL‐2 at 500 and 250 μg/ml, while no effect was observed at the 100 μg/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<0.05) IL‐2‐stimulated proliferation of PHA‐blasts at 500 and 250 μg/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 μg/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. This suggests that human trophoblast‐derived immunoregulatory factors that are present in hydatidiform mole inhibit human lymphocyte utilization of IL‐2 in a fashion similar to the murine (CTLL) model, and exhibit irreversible effects on lymphocytes containing high affinity IL‐2 receptors (PHA‐blasts) compared to lymphocytes with only low affinity IL‐2 receptors (resting T‐cell). This property of the trophoblast may partially explain how hydatidiform mole, and possibly pregnancy trophoblast in general, escapes lethal immunological challenge by the maternal immune system.