Marilen Benner

CHAPTER 2 34 The Th1, Th2, and Th17 cell profile is similar between endometrium and term deciduas It is suggested that successful pregnancy requires a delicate Th1/Th2/Th17/Treg balance (14). To investigate this balance, we classified CD4 + cells as Th1, nonconventional Th1 (Th1-like), Th2, or Th17 cells, based on the expression of the chemokine receptors CCR6, CXCR3, and CCR4 (37). Blood Th1-like cells were reported to have a mixed Th1/Th17 phenotype, i.e. production of RORC mRNA and IL-17, together with a higher production of TBX21 mRNA and IFN- γ than conventional Th1 cells, indicating higher Th1 activity (37). Th cell composition of MMC and DPMC were both different from PBMC, with significantly less Th2, and more Th1 cells in the uterine environment (Figure 4b). Between MMC and DPMC, percentages of Th1, Th2, Th17, and Th1-like cells did not differ significantly (Figure 4b). When investigating the intracellular cytokine expression profile after PMA/Ionomycin/Brefeldin stimulation, we observed a higher intrinsic capacity to express IFN- γ and IL-17 by DPMC CD4 + T cells (27.8%±15.4% and 4.4%±1.3% respectively) compared to CD4 + T cells from MMC (7.4%±3.3% and 2.6%±1.0% respectively), and also PBMC (7.5%±6.7% and 2.3%±1.3% respectively) (Figure 4d). In summary, a direct comparison between pre-pregnancy endometrium and term decidua reveals a activated immune signature, with more experienced conventional T cells and Treg. The distribution of Th subsets, defined by chemokine receptor expression patterns, did not differ significantly between endometrium and term decidua. However, the intrinsic capacity to produce IFN- γ and IL-17 was highest in term decidual CD4 + T cells, suggesting a possible role for both cytokines in the uterine environment during pregnancy. DISCUSSION Local decidual immune regulation is paramount to successful pregnancy. Previous studies investigating the phenotype of immune cells in endometrium and decidua are fragmented, and limited to comparing immune cells in either endometrium or decidua with their counterparts in peripheral blood (7-9, 27, 33, 34). Here, we performed a cross-sectional study, directly comparing the immune cell composition and functional capacity of pre-pregnancy endometrium and term decidua using flow cytometric analysis. We show clear differences in immune cell composition, suggestive of immune cell differentiation over the course of pregnancy, i.e. more experienced and less naive T cells and Treg in term decidua compared to pre-pregnancy endometrium. Analysis of the Th1/Th2/Th17/Treg subset composition showed that, while the distribution of Th1, Th2, and Th17 cells did not differ between term decidua and endometrium, there was a preference for Th1 over Th2 cells in the uterine environment compared to peripheral blood. The role of T cells in pregnancy has been subject to various studies. T cells were shown to be a major cell population in both endometrium and decidua, but their function and antigen-specificity