ElsevierDifferential distribution of NK cells in decidua basalis compared with decidua parietalis after uncomplicated human term pregnancy
Introduction
Natural killer cells (NK cells) represent an important effector component of the innate immune system, able to produce immunoregulatory cytokines and to recognize and kill target cells [1]. Phenotypically characterized by the expression of CD56 and the lack of expression of CD3, there are two distinct subsets of NK cells defined as CD56dimCD16+CD3− and CD56brightCD16−CD3−. Ninety percent of NK cells in normal circulating peripheral blood have the classical phenotype of CD56dimCD16+CD3− and the remaining 10% are CD56brightCD16−CD3− [2].
In contrast to peripheral blood, CD56brightCD16−CD3− cells represent the major subset of NK cells in the uterus and are termed large granular lymphocytes or uterine NK cells 3, 4, 5, 6, 7, 8. Representing a unique population of cells in the nonpregnant and pregnant endometrium, these CD56brightCD16− cells have prominent cytoplasmic granules 9, 10, are minimally cytotoxic yet highly proliferative 11, 12, produce a number of cytokines 13, 14, 15, 16, and express a wide variety of NK and cytokine receptors and adhesion molecules [17]. Although the specific role of these cells is still unknown, it is suggested that they regulate placental development by mediating maternal mucosal and arterial function and fetal extraembryonic trophoblast invasion [18].
Changes in CD56brightCD16− NK cells occur throughout the menstrual cycle and pregnancy. In the late secretory phase of the menstrual cycle, these cells become a prominent population of endometrial leukocytes in preparation for a possible conception 4, 5, 6, 7. Concurrently, the uterine mucosa begins to undergo decidualization, a hormone-dependent process in which endometrial stromal cells enlarge and become capable of producing growth factors and matrix components to support implantation and placental growth [19]. When pregnancy occurs, CD56brightCD16− NK cells account for up to 70% of the leukocytes at the site of implantation, identified as the decidua basalis 3, 20. The characteristic accumulation and predominance of these cells at the maternal-fetal interface at the beginning of the first trimester implies a putative role in the control of implantation and placentation. It is often stated that as pregnancy progresses, the number of uterine NK cells in the decidua basalis gradually declines or becomes virtually absent by term pregnancy [21]. Histologic studies in mice also indicate that the high proportion of uterine NK cells is limited only to early pregnancy 22, 23.
There are two distinct regions of the maternal-fetal interface where maternal decidua comes into direct contact with fetal extraembryonic tissue; one between decidua basalis and the invading interstitial trophoblasts, and the other between tissue lining the remainder of uterine cavity, identified as the decidua parietalis and the amniochorion (Figure 1). Although the decidua basalis encounters fetal tissue on the first day of implantation, contact between the decidua parietalis and fetal tissue does not occur until the end of the first trimester when fetal growth obliterates the uterine cavity. The focus of most immunologic studies has centered primarily on the decidua basalis, where immune interaction is expected to take place. Remarkably, the decidua parietalis has not been as well studied as the decidua basalis, yet it is an important site of the maternal-fetal interface. Our recent studies revealed that there are, in fact, significant differences in term decidua basalis and parietalis. Flow cytometric quantification of term decidual leukocytes exhibited a significantly higher percentage of T cells expressing CD25, human leukocyte antigen-DR (HLA-DR), CD45RO, and CD69 activation markers in decidua parietalis as compared to decidua basalis [24].
The aim of the present study was to quantify and compare the expression of CD16 and CD56 on leukocytes by flow cytometry and immunohistochemistry in normal term decidua basalis and parietalis.
Section snippets
Tissue specimens
Paired normal term decidua basalis and parietalis samples were obtained from 30 placentas following uncomplicated pregnancy. To exclude the effects of labor or vaginal delivery on the decidual cells, only placentas from pregnant women delivered by elective cesarean section prior to the onset of labor were selected. Parity ranged between 1 and 4. All women received spinal anesthesia prior to cesarean section. All cesarean sections were performed for breech presentation and resulted in the birth
Expression of CD16 and CD56 in normal term decidua basalis and parietalis
The percentage of several leukocyte subpopulations was examined in normal term decidua basalis and parietalis by flow cytometry (Figure 1 and summarized in Table 3). Comparison of the expression of CD16 and CD56 on leukocytes in these two tissue sites demonstrated a differential distribution (Figure 2). In decidua basalis, the percentage of CD56+ cells was significantly lower (22.8%, p < 0.0001) in comparison to that of decidua parietalis (41.2%). In contrast, the percentage of CD16+ cells was
Discussion
This study indicates that there are regional differences in the expression of CD16 and CD56 on leukocytes in term decidua basalis and parietalis. By precisely defining NK cell subsets, an analysis of NK cells in both term decidua basalis and term decidua parietalis was performed using flow cytometry and confirmed by immunohistochemistry. A higher percentage of CD56bright CD16− uterine NK cells was found in decidua parietalis in comparison with decidua basalis. In contrast, the percentage of CD56
Acknowledgements
We thank Prof. G.J. Fleuren and E. Dreef from the Department of Pathology of the Leiden University Medical Center for performing the immunohistochemistry.
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