Inhibition of lymphocyte proliferation by ovine trophoblast protein-1 and a high molecular weight glycoprotein produced by the peri-implantation sheep conceptus.
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abstract
Sheep conceptuses were flushed from uteri on day 16 of pregnancy and cultured in vitro. Three peaks of immunosuppressive activity (i.e., ability to inhibit [3H]thymidine incorporation into mitogen-stimulated lymphocytes) were localized in conceptus-conditioned culture medium: one corresponding to a high-molecular-weight glycoprotein (HMWG; Mr = 800-900 kDa), one corresponding to ovine trophoblast protein-1 (oTP-1), the antiluteolytic, interferon-like molecule of the sheep conceptus, and a third fraction containing a previously undescribed molecule with a molecular weight between 10 and 14 kDa. Both HMWG and oTP-1 inhibited lymphocyte proliferation in a dose-dependent manner. Delaying the addition of HMWG or oTP-1 until 24 h after the addition of phytohemagglutinin (PHA) reduced the degree of suppression relative to cultures where HMWG and oTP-1 were added at the time of PHA addition. Nonetheless, the molecules were still capable of inhibiting proliferation. Addition of human recombinant IL-2 (0-65 U/ml) to PHA-stimulated lymphocyte cultures could not reverse HMWG- or oTP-1-induced suppression of [3H]thymidine uptake by PHA-stimulated cells. Furthermore, treatment of lymphocytes with HMWG or oTP-1 suppressed IL-2-induced proliferation. Therefore, HMWG and oTP-1 affect both early and later events in the in vitro proliferative response of mitogen-stimulated lymphocytes, including responsiveness to IL-2.
