Marilen Benner

SUMMARY AND DISCUSSION 221 8 a chemokine receptor-based characterization (15). A limitation of this approach may be that as this phenotypical assignment has been established for peripheral blood lymphocytes, marker expression might not always refer to cells of equal functional characteristics when examining mucosal tissue. We observed relatively more Th1 compared to Th2 cells in uterine samples, which is in accordance with previous data (16). Comparing non-pregnant endometrium and decidua at term, we observed no significant change in levels of Th1, Th1-like, Th2, and Th17 cells. However, in this study, we only examined the pregnant mucosa at the very end of gestation. Pregnancy complications such as PE and RPL, manifest in the first trimester, during spiral artery remodeling. Thus, if fetal/paternal antigens or other possible triggers induce changes in Th profiles during the peri-implantation period, this cannot be conclusively investigated with this approach that lacks observations of early pregnancy. The discovery of immune subsets and immune-modulatory molecules continues. Measuring a broad range of cytokine profiles can directly point out pro- or anti-inflammatory trends. Indeed, recurrent implantation failure after ART has been associated with dysregulated uterine profiles of soluble factors (17). Analyzing endometrial cells obtained from menstrual blood of healthy, fertile women offers a way to research profiles of healthy, fertile women in future approaches. In the work presented in this thesis, we sought to exemplify that healthy pregnancy, much like the immune response in general, depends on the interaction of cells and soluble factors, rather than a particular type of cell that, on its own, determines the faith of gestation. The initial, exploratory study described in Chapter 2 led us to question what other possible key immune-modulators are involved in pregnancy that fulfill roles beyond our current understanding. THE DECIDUA CONTAINS SPECIALIZED REGULATORY CELLS: REGULATORY T CELLS A major focus in studying the maintenance of tolerance at the fetal-maternal interface has been put on Treg cells. We observed that compared to non-pregnant endometrium, frequencies of CD4 + CD25 Hi were increased in term decidua (Chapter 2) . This is in line with previously reported high levels of functional CD4 + CD25 Hi T cells with suppressive capacities and in vitro experiments confirming an induction of CD4 + Foxp3 + Treg upon co-culture with EVT (18-20). However, additional to a phenotypic overview in Chapter 2 , functional assays are needed to confirm if the observed T cell subset is truly regulatory, i.e. suppressive. The number of studies assessing functional capacities of decidual T cells with a regulatory phenotype is limited (18, 21, 22).