P-5
Fetus as a Successful Semiallogenic Graft
Hong-Nerng Ho, MD.
Department of Obstetrics and Gynecology, National Taiwan University, College of Medicine and Hospital, Taipei, Taiwan |
Several mechanisms are proposed for mother to accept the semiallogenic fetus in Mammal. Human endometrium contains a significant proportion of immunocytes. NK cells account for 60% of leukocytes in deciduas but their cytotoxicity was significantly less than that of the peripheral blood in normal pregnancy. Nevertheless, NK cytotoxicity significantly increases in anembryonic pregnancy but the proportion of decidual NK cells with particular KIRs (GL183 and EB6) decreases. This raises the possibility that these NK receptors may be involved in the rejection of fetus.
During pregnancy, the maternal immune response is biased toward Th2 polarity. We have analyzed cytokine production, both in vitro and in vivo, of peripheral and decidual T lymphocytes in normal and anembryonic pregnancies. Our data demonstrate that decidual T lymphocytes are Th2 predominant. When anembryonic pregnancy occurs, this Th2 predominance disappears.
IL-2 could stimulate the proliferation of CD4+ cells in autocrine fashion and leads to the paracrine activation of CD8+ cytotoxic T lymphocytes. Both decidual CD4+ and CD8+ T lymphocytes are activated during normal pregnancies, but the expression of CD25 was selectively decreased. The decrease in the expression of CD25 could lead to the decrease in cytotoxicity and tolerance of the fetus. Our study also reveals that the decrease in CD25 is not mediated by reduced mRNA production but by MMPs-mediated proteolytic process and it could be rescued by their inhibitor.
Treg cells (CD3+CD4+CD25 high) are a subpopulation of T cells that have regulatory function. These cells are significantly decreased in anembryonic pregnancy.
LIF knock out mice failed to achieve successful implantation. LIF expression varies with the menstrual cycle, peaking at the late secretory phase. Targeted disruption of the IL-11 receptor has defective deciduas in mice. Human studies consistently show that IL-11 and its receptor mRNA are expressed throughout the menstrual cycle. Nevertheless, in anembryonic pregnancy, the IL-11 is lower compared with normal pregnancy.
In summary, at the fetomaternal interface, the most abundant NK cells have decreased cytotoxicity. KIRs on decidual NK cells may suppress their cytotoxicity. The down-regulated Th1, up-regulated Th2 activity through cleavage of CD25 from the T cells, the increase in Treg cells and the alteration of cytokines, such as IL-11, may be parts of maternal immunomodulations for successful implantation in human.
|
