Mother’s little helpers: the immune cells that support pregnancy
3 May 2007
Scientists at the MRC’s Laboratory of Molecular Biology (LMB) had already shown that regulatory T cells, cells which regulate our immune system to prevent it overreacting, play an important role in preventing an immunological attack of fetuses in utero. Now they have demonstrated that these cells move into the uterus every 4 days in the time leading up to mice’s fertility peaks to prepare the host immune system for a potential pregnancy.
The discovery follows a number of investigations of the immunological reaction to pregnancy by the LMB team. Dr Alexander Betz and his colleagues have explored why the female uterus does not systematically reject the semi-foreign fetus which carries paternal antigens, potential targets for an immune attack. The first step in their work demonstrated the presence of high levels regulatory T cells in the uterus during pregnancy, without which the mother’s immune system would attack the fetus. Indeed, others have since shown that miscarriages often reveal very low levels of regulatory T cells.
The LMB scientists then found evidence that regulatory T cells started accumulating in the uterus prior to any pregnancy, as the female reaches her most fertile period. If a pregnancy then occurs and the regulatory T cells are exposed to paternal antigens, a sub-type of regulatory T cells capable of responding to the specific ‘threat’ posed continue to accumulate in the uterus throughout the pregnancy.
The team have now confirmed the cyclical accumulation of these regulatory T cells by looking at fluctuations of small proteins called chemokines in the uterus. These provoke the movement of regulatory T cells in specific directions and are thus able to retain the cells in the uterus. The levels of these chemokines raises and falls in line with the female cycle, accumulating in the run-up to the most fertile point in the cycle, and reducing afterwards.
However the presence of regulatory T cells is accompanied by the instinctive immune response to the semi-foreign foetus: effector T cells and it has also been shown that in periods of infection these are sometimes triumphant and prevent the implantation of the embryo. Evolutionarily, infections are not a good time to conceive and the avoidance of pregnancy may be in the mother’s best interest when she is ill.
Understanding the immune response to pregnancy sheds light on how it functions and balances itself and on the roles of different cells. Dr Betz believes that it might have been necessary for regulatory T cells to evolve, before nature took its next big step – the temporary implantation of the fetus in the mother’s womb. This in turn allowed fetuses to remain in the womb for longer and develop more before birth. This research could also help inform research into miscarriages.
“We feel that whilst the data is only of a descriptive nature, it beautifully illustrates the accumulation of cells in the tissue where they are likely to be needed. It suggests that every time the female becomes fertile the immune system anticipates a possible implantation event by strategically positioning the cells,” said Dr Betz.
Periodic Accumulation of Regulatory T Cells in the Uterus; Preparation for the Implantation of a Semi-Allogeneic Fetus? Marinos Kallikourdis and Alexander G. Betz is published in PLOS. DOI:10.1371/journal.pone.0000382
