Defective production of LIF, M-CSF and Th2-type cytokines by T cells at fetomaternal interface is associated with pregnancy loss

Development of CD4+ helper T (Th) cells into type 1 (Th1) or type 2 (Th2) effectors can be influenced by hormones enhanced during pregnancy. Progesterone, at concentrations comparable to those found at fetomaternal interface, promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-gamma by T cells. Furthermore, Th1-type cytokines promote allograft rejection and, therefore, may compromise pregnancy, whereas Th2-type cytokines, which inhibit Th1 responses, may allow allograft tolerance. In addition, T cell production of Leukemia Inhibitory Factor (LIF) and macrophage-stimulating factor (M-CSF), which are essential for embryo implantation and development, are up-regulated by IL-4 and progesterone. Finally, a direct cause-and-effect relationship between the defective production of LIF, M-CSF and Th2-type cytokines by T cells present at feto maternal interface and the pregnancy loss has been observed.