Inhibition of lymphocyte proliferation by ovine trophoblast protein-1 and a high molecular weight glycoprotein produced by the peri-implantation sheep conceptus.
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.
Newton
G R
GR
Department of Dairy Science, University of Florida, Gainesville 32611-0701.
Vallet
J L
JL
Hansen
P J
PJ
Bazer
F W
FW
D000818:Animals; D001755:Blastocyst / Q000032:analysis*; D003864:Depression, Chemical; D005260:Female; D006023:Glycoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D007370:Interferon Type I; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008970:Molecular Weight; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D012756:Sheep / Q000196:embryology
D006023:Glycoproteins; D007370:Interferon Type I; D007376:Interleukin-2; D011257:Pregnancy Proteins; C020947:interferon tau