A brief review of recent data on some cytokine expressions at the materno-foetal interface which might challenge the classical Th1/Th2 dichotomy.

Focussing attention on cytokines at the materno-foetal interface represents one of the major advances made in the field. This owes much to the visionary views of Tom Wegmann, and to the changes brought about in the field by immunotrophism and Th1/Th2 paradigms. We review these briefly and also point out some emerging problems.However, a certain number of newly discovered cytokines do not fit into the classical Th1/Th2 dichotomy. Yet, by their capacity to activate or downregulate NK cells, by their action on adhesion molecules, and by their regulatory effects on the vascularisation process, they are of possible interest within the materno-foetal relationship. Therefore, as a first step, we have undertaken a systematic study of the expression of IL-11, IL-12, IL-13, IL-15, IL-16, IL-17 and IL-18 in the uterus, the peri-implantation embryo, and later on decidual and placental tissues throughout pregnancy. These cytokines were detected in every case, with, in each case, a precise localisation, which will be detailed, and which indeed suggests important regulatory functions, especially during implantation. In some cases, as will be shown in the peri-implantation uterus, those cells are perfectly expressed by uterine GMG-NK-like cells. Comparative ELISAs and quantitative RT-PCR have been or are being conducted, but already the expression patterns that are observed, and the very precise window of appearance that is observed for some of the GMG NK-like cells, either around or in the implanting embryo, as well as the complexity of the respective distributions, strongly suggest that, as useful as it certainly was for a while, the Th1/Th2 paradigm must now be considered as an over-simplification. Rather, the existing data point to sequential windows and are suggestive of a system where an extreme complexity is allied to very precise timing and tuning. They also suggest that the materno-foetal relationship is not simply maternal tolerance of a foreign tissue, but a series of intricate mutual cytokine interactions governing selective immune regulation and also control of the adhesion and vascularisation processes during this dialogue.

New insights into maternal-fetal interactions at implantation.

The immunotrophic theory was enunciated by Tom Wegmann. Since then, the involvement of cytokines in implantation and materno-fetal tolerance has emerged as a central topic in reproductive immunology. This brief survey covers the historical background leading to the specification of the crucial role of cytokines at the feto-maternal interface, and the present known patterns of their function. Focus is addressed to the most recent concept, e.g. pregnancy as a Th2 phenomenon (the immune response of the mother is biased towards the production of anti inflammatory cytokines, amongst them IL-10 which suppress inflammatory responses). A brief description of the role of inflammatory cytokines in implantation is presented to explain why it does not fit into such a scheme, and other recent data, for example on gamma interferon, also fails to accord with the Th2 phenomenon.