Endocrine Abstracts

The survival of the semiallogeneic fetus within the mother is thought to be due to mechanisms of immunological tolerance. Regulatory T cells (Treg) are believed to have a crucial role in maintaining pregnancy by creating a transient tolerant microenvironment within the maternal uterus as former studies confirmed. We have evidences that Treg expand in lymph nodes from normal pregnant mice already on day 2 of pregnancy. Abortion-prone mice present diminished numbers of Treg in immune organs throughout pregnancy. As both pregnancy combinations (normal pregnant and abortion-prone mice) present similar levels of progesterone, estriol and estrone, hormones do not seem to be involved in Treg expansion. However, they may be involved in their recruitment into the vaginal lumen.

An enormous augmentation in the number of TCRαβ⁺CD4⁻CD8⁻foxp3⁺ cells in vaginal mucus from normal pregnant animals already on day 0.5 after conception, followed by an increase in Treg numbers in lymph nodes, suggest that Treg need to be activated by male antigens for being protective. The antigen presentation would take place in the periphery e.g. in vaginal mucus, the first site of contact with paternal antigens, directly after insemination as we could confirm by identifying paternal antigens and paternal APCs at this site. This explains previous observations on Treg transfer being effective in preventing abortion if done on days 0–2 of pregnancy but not later. Interestingly, mating CBA/J females with vasectomized BALB/c males generated foxp3⁺ cells in lymph nodes draining the uterus, while pseudopregnancy induced by mechanical stimulation did not. Treg-induced tolerance is transient, as Treg came back to the normal levels after the disappearance of the paternal/fetal antigens, 14 days post-partum.

The molecules responsible for Treg recruitment immediately after copulation are being currently studied in our laboratory. Besides, running clinical studies will help us clarifying whether similar pathways are taking place in humans.