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.
Assal-Meliani
A
A
CJF INSERM 92-09, Biologie Cellulaire et Moléculaire de la Relation Materno-Fetale, Batiment de Gynécologie Obstétrique, Hôpital Antoine Béclère, Clamart, France.
Charpigny
G
G
Reinaud
P
P
Martal
J
J
Chaouat
G
G
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007370:Interferon Type I; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010835:Phytohemagglutinins / Q000494:pharmacology; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
D007166:Immunosuppressive Agents; D007370:Interferon Type I; D010835:Phytohemagglutinins; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C020947:interferon tau; D007371:Interferon-gamma