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Visualizing tolerance induction: behavior and function of regulatory T cells during the establishment of materno/fetal tolerance (VISTO)
Start date: Mar 1, 2012, End date: Feb 28, 2014 PROJECT  FINISHED 

The presence of foreign (allogenic) tissue in a host yields an immune response with the goal to destroy the tissue. During pregnancy, however, the semiallogenic fetus is allowed to grow within the maternal uterus. This ‘immunological paradox of pregnancy’ has received much attention because of its therapeutic implications in organ transplantation and autoimmune diseases.While it has recently been established that regulatory T cells are essential in establishing tolerogenic conditions during pregnancy, little is known about where and when T regulatory act.I will characterize, using transgenic mouse lines and intra-vital two photon microscopy, the spatio-temporal characteristics of T regulatory cell recruitment at the materno/fetal interface. I will analyze the dynamics of cellular interactions between T regulatory cells with other immune system cells under physiological conditions and in a mouse model of spontaneous abortion. Finally, I will use a candidate gene approach to reveal similarities between molecular mechanisms of materno/fetal tolerance and tumor immune escape.A better understanding of the mechanisms leading to materno/fetal tolerance will have therapeutic implications for the treatment of patients with recurrent spontaneous abortion and pre-eclampsia, for organ transplantation and for autoimmune diseases. Moreover, the interdisciplinary comparison of similarities between materno/fetal tolerance and tumor immune escape will provide novel experimental approaches for tumor immuno-therapy.
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