The interferon system in the developing mouse embryo and in differentiating teratocarcinoma cells.

A modified assay to detect interferon production from individual cells has been designed which is more accurate than those already described. Use of this modified assay has demonstrated that the difference between cell lines that can be induced to produce high yields of interferon, and those which are only capable of producing low yields of interferon, resides in the number of individual cells able to produce interferon in that culture. Thus the apparent homogeneous response of a cell culture to an interferon inducing agent, masks the heterogeneous response of the individual cells which make up that culture. This modified assay is probably sensitive enough to detect all cells capable of producing interferon within a given cell population; and the data presented in section one suggests that this assay can be used with confidence to assay interferon production in cell systems which only produce small amounts of interferon. Cloned 'nullipotent' embryonal carcinoma (ec) cells, like the pluri- potent ec cells described by Burke et al (1978), do not possess an active interferon system, and it is proposed that such cells lack the ability to produce interferon mRNA in response to an interferon-inducing agent. When these 'nullipotent' ec cells are treated with retinoic acid they show an activation of the interferon system which extends for approximately ten to fifteen days. The extent of activation seen varied between different embryonal carcinoma cell lines. In these differentiating cultures there is a parallel increase, both in the percentage of individual cells able to produce interferon, and in the yield of interferon per producer cell. The percentage of single cells able to produce interferon always remained small compared to the non-producer cell3 in the culture. The pattern of development of interferon inducibility and sensitivity does not distinguish between the different types of endoderm-like cell generated by the various differentiating teratocarcinoma cell lines, nor can the amount of interferon produced by different cell lines be used to quantitate the extent of differentiation which has occurred. However, the activation of the interferon system; because it coincides with changes in morphology and in protein synthesis, can be used as an additional positive marker for the production of differentiated cells in this system. The data presented in section three demonstrates that during the first third of pregnancy the embryo is unable to produce interferon in response to a virus infection, and furthermore suggests that the antiviral action of interferon may be non-specifically inhibited by the tissues of the reproductive system from the adult female mbuse. A functional interferon system develops during the seventh day of embryonic development, and the embryonic ectoderm and the visceral extra- embryonic endoderm are the last tissues to show a lack of interferon inducibility. Thus, the mouse embryo can be seen to become capable of mounting an interferon-based antiviral response during a period when it is unable to mount a humoral and cell mediated antiviral immune response. This factor may be of importance in the reduced susceptibility to the pathogenic effects of virus infections, which is a feature of the mid to late term mammalian embryo.