Towards improving pregnancy success rates: Understanding the functional role and memory development of CD4+ regulatory T cell subsets during first and second pregnancies.

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A previous successful pregnancy significantly reduces the risks for complications in subsequent pregnancies, such as spontaneous abortions, perterm birth or pre-eclampsia. Biological pathways mediating this decreased risk for pregnancy complications, despite the advanced age of the mother, are currently unknown. In the present application, we seek to identify immune markers that may account for the higher odds for successful secondary pregnancies. We will focus on the role of CD4+ regulatory T cell subsets during and between first and second pregnancies. In a basic science approach, we will utilize a variety of loss-of-function mouse models and propose objectives to test the causality between CD4+ regulatory T cell subsets and the outcome of pregnancy in step-wise, experimental functional analyses. The fate of CD4+ regulatory T cell subsets and their acquisition of memory functions is a pivotal aspect of the proposed work program. Moreover, biological samples from pregnant women during their first and second pregnancy are available to us (n=48), which shall be used to apply the findings from our basic science approach and test their relevance as diagnostic tools. We envision that these insights will allow us to generate a solid foundation on which diagnostic and therapeutic avenues can be advanced, aimimg to enhance the odds for healthy (first) pregnancies.