Assal-Meliani A, Charpigny G, Reinaud P, Martal J, Chaouat G
CJF INSERM 92-09, Biologie Cellulaire et Moléculaire de la Relation Materno-Fetale, Batiment de Gynécologie Obstétrique, Hôpital Antoine Béclère, Clamart, France.
J Reprod Immunol. 1993 Nov;25(2):149-65. doi: 10.1016/0165-0378(93)90055-m.
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.
绵羊滋养层蛋白(oTP)是一种20 kDa的胚胎分泌产物,在妊娠第12至22天由绵羊孕体滋养层组成性分泌。氨基酸测序和分子克隆显示它与2类α亚家族的干扰素具有结构相似性,定义了tau干扰素组。它具有典型的类干扰素生物学活性。通过基因工程生产的重组绵羊滋养层蛋白(roTP)经阴离子交换高效液相色谱法纯化至高度均一(98%)。它在免疫检测和抗病毒活性测定中的表现与天然形式相似。我们在此表明,当在PHA刺激的小鼠、人和绵羊淋巴细胞增殖实验中进行检测时,roTP具有免疫抑制作用。它还抑制单向和双向的小鼠和人混合淋巴细胞反应(MLR)。由于天然oTP至少有5种异构体,我们也检测了它们的免疫抑制活性。所有异构体均抑制PHA刺激的人和绵羊淋巴细胞生成。最后,通过淘选法进行绵羊CD4+和CD8+ T细胞分选。与早期在人淋巴细胞上检测roTP活性的观察结果相反,在PHA刺激的增殖实验中,绵羊CD4和CD8 T细胞亚群对roTP均敏感。因此,有人提出滋养层干扰素可能在防止早期胚胎因免疫排斥而死亡方面具有重要作用,至少在绵羊物种中是如此。