REGULATION OF UTERINE IMMUNE FUNCTION BY PROGESTERONE - LESSONS FROM THE SHEEP

Survival of the fetal allograft results from orchestrated adjustments in activity of maternal lymphoid cells as well as in trophoblast gene expression. One molecule that regulates uterine immune responsiveness is progesterone. In fact, uterine skin graft survival and susceptibili ty to bacterial infections are increased by progesterone. This review focuses on the role of progesterone in regulation of uterine immune fu nction in the sheep. While the importance of progesterone as a regulat or of immune function likely varies between species, concepts derived from the sheep model may prove pertinent to other species also. The ac tions of progesterone on uterine immune function in the ewe change dur ing pregnancy. Before day 50 of gestation, i.e. when the uterus is sti ll dependent upon the corpus luteum as a source of progesterone, conce ntrations of progesterone are probably not high enough at the maternal -fetal interface to inhibit lymphocyte activation. During this early p eriod of pregnancy, progesterone inhibits uterine immune function by i nducing endometrial secretion of a protein called uterine milk protein (UTMP) that itself is inhibitory to lymphocyte function. After day 50 of pregnancy, it is likely that the placenta produces sufficient amou nts of progesterone to directly inhibit lymphocyte proliferation. Addi tional inhibition is achieved because of sustained synthesis of UTMP. Accordingly, progesterone acts to regulate uterine immune function in ways that allows for inhibition of immune responses at the utero-place ntal interface without systemic immunosuppression. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.