Uterine (CD56+) Natural Killer Cells Recruitment: Association with Decidual Reaction Rather than Embryo Implantation

Abstract

Whether decidual leukocyte recruitment and/or increase is primarily hormonally regulated or induced mainly by blastocyst implantation is a matter of debate. Thus, this study investigated the number and distribution of leukocyte populations, with emphasis on natural killer (NK) cells of uterine and peripheral type, within decidual tissue from women with decidualized endometrium both related and unrelated to pregnancy and those with ectopic decidua associated with intrauterine pregnancy, as well as in tubal implantation sites. Immunohistochemical characterization of immune cells using antibodies to CD3, CD4, CD8, CD20, CD68, CD16, CD56, CD57, in formalin-fixed, paraffin-embedded tissue, and a quantitative analysis of these subpopulations was conducted in tissue blocks from four groups of patients: (i) 20 women with decidualized endometrium due to progestin therapy (i.e. not associated with gestation) (group Prog-D); (ii) 20 women with intrauterine pregnancy-associated ectopic decidua (seven in the Fallopian tube, five in the ovary, five in the uterine cervix, and three in the omentum) (group Ect-D); (iii) 20 women with spontaneous abortion who had an histologic sample of the decidua at the uterine implantation site (group Uter-D); and (iv) 20 consecutive patients who had had an ectopic tubal pregnancy (group Tub-Preg). Twenty gynecologic specimens with marked inflammatory reaction were used as controls (group Con). CD3+, CD4+, CD8+, CD68+ cells were detected in all tissue samples investigated. In contrast, CD20+ cells were detected in all samples in group Con, but only in 75%, 25%, 55% and 70% of groups Prog-D, Ect-D, Uter-D and Tub-Preg, respectively. In all tissue samples investigated, CD57+ and CD16+ cells were detected. Conversely, CD56+ cells were completely absent in 15 of 40 cases (37.5%) lacking decidual reaction (group Tub-Preg, 7/20; group Con, 8/20) but were present in all cases showing decidual reaction. In contrast with CD56+ cells, CD57+ NK cells were more abundant in group Con than in the four study groups. CD56+ NK cells are closely related to decidua irrespective of its eutopic or ectopic location rather than to the implantation site. This suggests that the recruitment and/or increase of uterine NK cells into the uterus is not dependent on the physical presence of an implanting embryo but instead is controlled hormonally.