La Bonnardière C
Unité de Virologie et d'Immunologie Moléculaires, INRA, Jouy en Josas, France.
J Reprod Fertil Suppl. 1993;48:157-70.
In several ungulate species, the preimplantation trophoblast, among various secretions, produces large amounts of antiviral activity that was identified as interferon (IFN). IFNs (types I and II) are pleiotropic cytokines, which in addition to a potent antiviral activity, exert multiple effects on cell growth and differentiation, in particular on the cells of the immune system. In ruminants, trophoblastic IFN, or trophoblast protein-1 (TP-1), was found to consist of a multigenic family related to type I IFN-omega. These IFNs exert hormone-like effects through receptors present on the endometrium, leading to the prolongation of luteal life-span and hence to sustained progesterone secretion. In pigs, a species in which the maternal recognition of pregnancy is controlled by conceptus-derived oestrogens, two IFNs have been found in the preimplantation trophoblast. The major species is IFN-gamma (type II), that so far had been found only in activated T lymphocytes and natural killer (NK) cells. Transcription of the IFN-gamma gene in the pig trophoblast differs from that in mature lymphocytes, since two mRNAs are present. The other component with antiviral activity is a novel type I IFN, distant in sequence from IFN-alpha, beta, omega, and containing seven cysteines in its deduced mature protein. These two unrelated IFNs are temporally co-induced, with maximal secretion at day 16 of pregnancy. Specific receptors for both IFNs have been found on endometrial epithelial cells, but not on the preimplantation trophoblast, suggesting a paracrine effect on the uterus. Different hypotheses as to their role(s) in the establishment or maintenance of implantation are discussed. Whereas an indirect anti-infectious (antiviral) protection of the conceptus by IFNs cannot be ruled out, arguments are presented that do not favour a role in the immune tolerance of the conceptus.
在几种有蹄类动物中，植入前的滋养层细胞在多种分泌物中会产生大量抗病毒活性物质，该物质被鉴定为干扰素（IFN）。干扰素（I型和II型）是多效性细胞因子，除了具有强大的抗病毒活性外，还对细胞生长和分化，特别是对免疫系统的细胞发挥多种作用。在反刍动物中，滋养层干扰素，即滋养层蛋白-1（TP-1），被发现是由一个与I型ω干扰素相关的多基因家族组成。这些干扰素通过子宫内膜上存在的受体发挥类似激素的作用，导致黄体寿命延长，从而使孕酮持续分泌。在猪这个物种中，母体对妊娠的识别由孕体来源的雌激素控制，在植入前的滋养层细胞中发现了两种干扰素。主要的一种是γ干扰素（II型），到目前为止仅在活化的T淋巴细胞和自然杀伤（NK）细胞中发现过。猪滋养层细胞中γ干扰素基因的转录与成熟淋巴细胞中的不同，因为存在两种mRNA。另一种具有抗病毒活性的成分是一种新型I型干扰素，其序列与α、β、ω干扰素相距甚远，在推导的成熟蛋白中含有七个半胱氨酸。这两种不相关的干扰素在时间上共同诱导产生，在妊娠第16天分泌量最大。在子宫内膜上皮细胞上发现了这两种干扰素的特异性受体，但在植入前的滋养层细胞上未发现，这表明它们对子宫有旁分泌作用。文中讨论了关于它们在植入建立或维持过程中作用的不同假说。虽然不能排除干扰素对孕体有间接抗感染（抗病毒）保护作用，但也提出了一些不支持其在孕体免疫耐受中起作用的观点。
