Relationship between the cytotoxic activity of peripheral blood natural
killer cells and recurrent miscarriage
Abstract
Peripheral blood natural killer (pNK) cells can be recruited by the
endometrium to participate in the decidualization and be in contact with
the villus in the intervillous space during pregnancy. Moreover, pNK
cells can exert cytotoxicity to cytotrophoblast, especially in abnormal
pregnancy. However, it is still controversial about the association
between pNK cytotoxicity and RM so far. In this study, we aim to compare
the percentage, immunophenotype and function of pNK cells between
patients with RM and fertile controls. The peripheral blood was
collected from 49 patients with RM and 11 fertile women in their middle
luteal phase of the menstrual cycle. pNK cells were co-cultured with
K562 cells at three different cell ratios to measure the cytotoxicity.
The percentage of CD3-CD56+ pNK was analyzed by flow cytometry and
quantified to evaluate the expression of cytotoxic granules (granzyme B,
granulysin, and perforin), and the cell surface receptors related to pNK
cell cytotoxicity (NKG2D, NKp30, NKp46, CD158a, CD158b) were also
detected. The general linear model analysis showed that pNK cell
cytotoxicity in patients with RM was significantly lower than that in
fertile controls. The RM group possessed a significantly lower level of
granzyme B+ pNK cells and significantly higher level of CD158a+, CD158b+
pNK cells than that in the control group. However, there was no
significant difference in the proportion of circulating CD3-CD56+ NK
cells expressing the granzyme B, granulysin, perforin, NKG2D, NKp30,
NKp46, CD158a, CD158b. Our results suggested that a lower pNK
cytotoxicity might be associated with RM.