Summary NK cell activity has been detected in the early murine decidua, and hypothesized to be mediated by granulated metrial gland (GMG) cells. The possibility that natural cytotoxic (NC) cells are also present in the decidua has not been investigated. In this study mAb to NK cells (anti‐NK‐1.1) and NC cells (anti‐NC‐1.1) were used to characterize the decidual cells of days 8–14 pregnant (CBAxC57BL/6) Fl mice. Flow cytometric and immunohistological analyses showed predominantly NK‐1.1+ and NC‐1.1+ large and granular single nucleated decidual cells with abundant cytoplasm. A ‘bright’ and a ‘dim’ subset were identified for both NK‐1.1+ and NC‐1.1+ cells. The NC‐1.1dim and NK‐1.1dim cells increased in number and size as pregnancy progressed. When tested in 51Cr‐release assays, the decidual cells showed significant levels of both NK and NC activities which increased with progression of pregnancy. The NK and NC activities were partially inhibited (47 and 34%) by preincubation of the decidual cells with anti‐NC‐1.1 and complement (C), or anti‐NC‐1.1 alone. Results indicate that natural cell‐mediated cytotoxicity in the decidua is in part, at least, mediated by NK‐1.1+ and NC‐l.l+ cells, and that the NK‐1.1dim and NC‐1.1dim cells are very likely to be GMG cells. This is the first report of NC cells in the mouse uterus.

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Murine natural cytotoxicity, which is a major component of the innate immune response in cancer, is mediated by leukocytes that express the NC-1.1 receptor. Mice depleted of natural cytotoxicity by treatment with an anti-NC-1.1 mAb show enhanced growth of certain transplantable tumors, so agents that enhance natural cytotoxicity by NC-1.1+ cells have the potential to be effective anticancer therapeutic agents. We have examined the immunomodulatory effect of levamisole on natural cytotoxicity mediated by NC-1.1+ cells against the BALB/c WEHI-164 murine fibrosarcoma. Administration of levamisole to BALB/c mice significantly enhanced in vitro splenic natural cytotoxicity against 51Cr-labeled WEHI-164 tumor cells. The effect was most marked 48 h after levamisole treatment, at a dose of 10 mg/kg body weight. This enhancement of natural cytotoxicity by levamisole could be completely abrogated by pretreatment of mice with an anti-NC-1.1 mAb. Treatment of BALB/c mice with 10 mg/kg levamisole significantly reduced the growth of WEHI-164 and this effect was abrogated by pretreatment of mice with anti-NC-1.1, indicating that the antitumor effect of levamisole was mediated, at least in part, via NC-1.1+ cells.

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