Regulation of fetal allograft survival by hormone-controlled Th1- and Th2-type cytokines

There is clear evidence to suggest that the maternal immune system during pregnancy can enhance or inhibit the development of the fetoplacental unit. Recent data support the view that some cytokines produced by both T cells and non-T cells (IL-3, GM-CSF, TGF-P, IL-4, IL-10), favor fetal survival and growth. In contrast, other cytokines, such as IFN-gamma, TNF-beta and TNF-alpha, can rather compromise pregnancy. Accordingly, we show here that T-cell clones generated from the decidua of women with unexplained recurrent abortion produced significantly lower concentrations of IL-4 than clones derived from the decidua of voluntary abortions or the endometrium of nonpregnant women. Thus, despite the complexity of the cytokine network, it appears that cytokines favoring the maintenance of fetal survival mainly belong to the Th2 pathway, whereas the failure of pregnancy rather associates with the predominance of Th1-type cytokines and/or the absence of Th2-type cytokines. Interestingly, we also found that, at least in vitro, progesterone promotes the preferential development of Th2-like cells and induces transient IL-4 production by established Th1 cells, whereas relaxin, another corpus luteum-derived hormone, mainly promotes the development of Th1-like cells. These data provide an excellent basis for investigating the relationship between the endocrine and the immune system in the regulation of the maternal-fetal interaction.