Natural killer cell activity of lymphocytes exposed to ovine, type I, trophoblast interferon.
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PROBLEM: A member of newly described interferon (IFN) family, ovine trophoblast protein one (oTP-1, now named as ovine type I trophoblast interferon, oTIFN), is a major secretory product of sheep conceptuses during days 11-21 of pregnancy. Type I trophoblast IFN shares high amino acid and nucleotide sequence homology with other mammalian IFN-alpha s and has functional characteristics of IFNs such as antiproliferative, immunosuppressive, and antiviral activities. Moreover, oTIFN is responsible for the antiluteolytic signaling for early pregnancy recognition in sheep. It has been reported that natural killer (NK) cells are recruited to the pregnant uterus and contribute para-immunotrophic effects on growth and differentiation of the conceptus (embryo/fetus and associated membranes). Because IFNs are potent modulators of NK cell activity, the present study examined interactions between oTIFN and sheep and pig NK cells. METHODS: A 51Cr release assay was used to evaluate the effects of various concentrations of oTIFN and IFN-alpha on sheep and pig NK cell activity against K562 and HeLaS3 cells in vitro. Dosages were tested at four effector to target cell ratios. RESULTS: These data provide the first evidence that oTIFN is a potent NK cell activator in vitro. Recombinant human IFN-alpha 1 (rhIFN-alpha) and oTIFN increased (P < 0.01) ovine NK cell cytotoxicity for K562 cells at very low dosages (50 antiviral units (AVU)/ml). Lower doses of oTIFN (15 AVU/ml) were sufficient (P < 0.01) to enable sheep NK cells to kill ovine NK resistant cells, HeLa S3, in a dose-dependent fashion. However, much higher concentrations (> 400 AVU/ml) of oTIFN were needed to increase (P < 0.01) porcine NK cell cytotoxicity. This suggests that oTIFN has some species specificity in activating NK cells. The augmentation of NK cell activity by 100 AVU/ml of oTIFN was effectively neutralized by an anti-oTIFN monoclonal antibody (HL-98) at a dilution of 1:800. CONCLUSIONS: Results of the present study clearly indicate that oTIFN is as active as rhIFN-alpha 1 for activating NK cells in vitro. Immune cells, especially those recruited to the pregnant uterus by conceptus secretory products, may be stimulated/activated by trophoblast IFNs. However, the function of activated NK cells during early pregnancy remains to be determined.
