RECOMBINANT OVINE TROPHOBLASTIN (ROTP) INHIBITS OVINE, MURINE AND HUMAN LYMPHOCYTE-PROLIFERATION

Ovine trophoblastic protein (oTP) is a 20-kDa embryonic secretory product constitutively secreted by ovine conceptus trophoblast from days 12-22 of pregnancy. Amino acid sequencing as well as molecular cloning revealed it to bear structural analogies with interferons of the class 2 alpha subfamily, defining the tau interferon group. It is endowed with classical interferon-like biological activities. Recombinant ovine trophoblastin (roTP), produced by genetic engineering, was purified by anion exchange HPLC to a high degree of homogeneity (98%). It behaved in immunodetection and antiviral activity assays like the natural form. We show here that when assayed on PHA-driven murine, human, and ovine (sheep) lymphocyte proliferation, roTP is immunosuppressive. It also inhibits unidirectional and bidirectional murine and human mixed lymphocyte reactions (MLRs). Since natural oTP possesses (at least) 5 isoforms, we also assayed these for immunosuppressive activities. All of them inhibited PHA-driven human and ovine lymphoblastogenesis. Finally, CD4+ and CD8+ ovine T cell selection was performed by panning. In contrast with earlier observations assaying roTP activity on human lymphocytes, both ovine CD4 and CD8 T cell subsets were sensitive to roTP in a PHA-driven proliferation assay. It is therefore suggested that trophoblast interferons might have a strategic function in preventing early embryonic demise by immunologic rejection, at least in ovine species.