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

Ovine trophoblastic protein (oTP) is a 20-kDa embryonic secretory prod uct constitutively secreted by ovine conceptus trophoblast from days 1 2-22 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 w ith classical interferon-like biological activities. Recombinant ovine trophoblastin (roTP), produced by genetic engineering, was purified b y anion exchange HPLC to a high degree of homogeneity (98%). It behave d in immunodetection and antiviral activity assays like the natural fo rm. We show here that when assayed on PHA-driven murine, human, and ov ine (sheep) lymphocyte proliferation, roTP is immunosuppressive. It al so inhibits unidirectional and bidirectional murine and human mixed ly mphocyte reactions (MLRs). Since natural oTP possesses (at least) 5 is oforms, we also assayed these for immunosuppressive activities. All of them inhibited PHA-driven human and ovine lymphoblastogenesis. Finall y, CD4+ and CD8+ ovine T cell selection was performed by panning. In c ontrast with earlier observations assaying roTP activity on human lymp hocytes, both ovine CD4 and CD8 T cell subsets were sensitive to roTP in a PHA-driven proliferation assay. It is therefore suggested that tr ophoblast interferons might have a strategic function in preventing ea rly embryonic demise by immunologic rejection, at least in ovine speci es.