Peripheral Blood NK Cell Cytotoxicities are Negatively Correlated with CD8⁺ T Cells in Fertile Women but not in Women with a History of Recurrent Pregnancy Loss

Abstract

NK cell-mediated immunopathology plays a role in RPL. Women with RPL have a disrupted immune regulation between cytotoxic T and NK cells. Failure of immune modulation by CD8(+) T cells may exert NK cell activation and reproductive failures in women with RPL.

Modulatory effects of vitamin D on peripheral cellular immunity in patients with recurrent miscarriage

“…An increased number of peripheral NK cells is regarded as an important marker for RM . Peripheral blood NK cell activity was significantly decreased during early pregnancy compared to nonpregnant status . These results suggest that the decrease in NK cells and the suppression of NK cell activity may prevent a maternal alloimmune reaction to the fetus.…”

“…NK cells play a critical role in the establishment and maintenance of pregnancy and placental development . Circulating NK cells were found to be elevated both in percentage and cytotoxicity in RM patients . An increased number of peripheral NK cells is regarded as an important marker for RM .…”

“…Known risk factors for RM include genetic abnormalities, endocrine disorders, infectious diseases, and uterine anatomical malformations . According to recent publications, patients with RM tend to produce an abnormal level of CD19 + B cells and CD56 + NK cells, a predominantly Th1‐type response (IFN‐γ and TNF‐α), and an elevated NK cell cytotoxicity . Therefore, it is now widely accepted that immunological dysfunction may play a crucial role in the pathogenesis of RM …”

Increased Circulating Th1/Th2 Ratios But Not Other Lymphocyte Subsets During Controlled Ovarian Stimulation are Linked to Subsequent Implantation Failure after Transfer of In Vitro Fertilized Embryos

“…Aberrations of the circulating immune cells have been proposed to be responsible for recurrent miscarriage (RM), unexplained infertility, and repeated implantation failure (RIF). A Th1 cytokine bias, increased NK cell activity, or elevated percentages of peripheral blood lymphocyte subsets has been found with increased prevalence in these patients, compared with normal fertile women, suggesting that the systemic regulation of immune cells is directly related to the reproductive outcome.…”

Increased Toll-Like Receptor-Myeloid Differentiation Factor 88 Expression at the Maternal-Fetal Interface Is Associated with Spontaneous Abortion

“…Cytokines that are secreted by Th1 cells (e.g., IL-2, TNF-α, IFN-γ) will negatively affect embryonic implantation because trophoblasts are highly sensitive to these cytokines, and this can lead to apoptosis of trophoblast cells [46]. Our preliminary experiments also found that the Th1-type cytokines IL-2 and IFN-γ are highly expressed in the co-culture system of cells that come from the maternal-fetal interface in CBA/J × DBA/2 matings (unpublished data).…”