Evidence for a Role for the Adaptive Immune Response in Human Term Parturition

Abstract

PROBLEM Spontaneous labor at term involves leukocyte recruitment and infiltration into the choriodecidua; yet, characterization of these leukocytes and their immunological mediators is incomplete. The purpose of this study was to characterize the immunophenotype of choriodecidual leukocytes as well as the expression of inflammatory mediators in human spontaneous parturition at term. METHOD OF STUDY Choriodecidual leukocytes were analyzed by FACS, immunohistochemistry, and RT-PCR in three different groups: (i) preterm gestation delivered for medical indications without labor; (ii) term pregnancy without labor; and (iii) term pregnancy after spontaneous labor. RESULTS Two T-cell subsets of memory-like T cells (CD3+CD4+CD45RO+ and CD3+CD4−CD8−CD45RO+ cells) were identified in the choriodecidua of women who had spontaneous labor. Evidence for an extensive immune signaling network composed of chemokines (CXCL8 and CXCL10), chemokine receptors (CXCR1-3), cytokines (IL-1β and TNF-α), cell adhesion molecules, and MMP-9 was identified in these cells during spontaneous labor at term. CONCLUSIONS The influx of memory-like T cells in the choriodecidua and the evidence that they are active by producing chemokines and cytokines, and expressing chemokine receptors, cell adhesion molecules, and a matrix-degrading enzyme provides support for the participation of the adaptive immune system in the mechanisms of spontaneous parturition at term.

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

“…These results coincide with previous studies demonstrating that choriodecidual leukocytes express CAMs [16,39,40], cytokines [8,41,42], chemokines [16,34], and their receptors [16,34,43], enzymes [35,44,45], antimicrobial peptides [46], markers of activation [17,39,[47][48][49], and even hormone receptors [50] before and during the process of labor. Together, these findings demonstrate that the choriodecidual leukocytes are a rich source of inflammatory mediators that can participate in the proinflammatory milieu that accompanies the process of labor.…”

“…Labor is recognized as a physiological process of sterile inflammation [1][2][3][4][5], characterized by the infiltration of immune cells into the cervix [6][7][8][9], myometrium [8,[10][11][12], and maternal-fetal interface [8,[13][14][15][16]. This interface includes two areas of contact between the mother and the fetus: the decidua parietalis, which lines the uterine cavity not covered by the placenta and is juxtaposed to the chorion laeve; and the decidua basalis, which lays on the basal plate of the placenta and is invaded by the interstitial trophoblast [16,17].…”

“…This interface includes two areas of contact between the mother and the fetus: the decidua parietalis, which lines the uterine cavity not covered by the placenta and is juxtaposed to the chorion laeve; and the decidua basalis, which lays on the basal plate of the placenta and is invaded by the interstitial trophoblast [16,17]. Decidua parietalis is composed of stroma-type cells, glandular cells, and leukocytes [18][19][20][21], and the portion that is attainable is attached to the chorioamniotic membranes; therefore, this anatomical site is known as the choriodecidua [16]. Since the choriodecidua represents the major site of fetal antigenic exposure to the maternal immune system, our studies have focused on understanding the mechanisms whereby maternal leukocytes are recruited into the maternal-fetal interface and their role in the processes of term and preterm labor [22].…”

“…The current hypothesis is that the chorioamniotic membranes exhibit chemotactic processes driven by specific chemokines in order to recruit maternal circulating * Nardhy Gomez-Lopez nardhy.gomez-lopez@wayne.edu * Rodrigo Vega-Sanchez r.vega@inper.mx vegarodrig@gmail.com leukocytes into the choriodecidua [14,16,[23][24][25]. In addition, the responsiveness of peripheral leukocytes to be attracted to chemotactic stimuli derived from the chorioamniotic membranes seems to be a key feature in this process [26].…”

“…Collectively, these data suggest that the chorioamniotic membranes, and most likely the decidual stromal cells, recruit maternal circulating leukocytes into the choriodecidua prior to and during the process of labor. Following recruitment, the choriodecidual leukocytes expressed cell adhesion molecules (CAMs) [16,[31][32][33] and labor mediators including cytokines/chemokines [14][15][16]34] and matrix metalloproteinases (MMPs) [35]. All of which elicit cellmediated immune responses that participate in the process of labor [1,[36][37][38].…”