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

We aim to investigate NK cell cytolytic activities and its relationship to other lymphocyte subsets in peripheral blood of women with a history of recurrent pregnancy loss (RPL). Women with a history of RPL (n = 48) comprised RPL group, and 15 fertile women served as controls. Lymphocyte subsets such as T (CD3(+)), T helper (CD3(+)/4(+)), cytotoxic T (CD3(+)/8(+)), NK (CD3(-)/56(+)), and peripheral blood NK cell cytolytic activities at three different effector to target cell ratios (E/T ratio, 50:1, 25:1 and 12.5:1) are measured by flow cytometric analysis. Peripheral blood NK cell levels are significantly increased in women with RPL as compared to controls (P = 0.001). NK cell cytolytic activities in RPL group are significantly increased as compared to those of controls at E/T ratio of 50:1 (42.5 ± 16.3 versus 29.9 ± 13.8, P = 0.009), 25:1 (31.6 ± 15.0 versus 19.4 ± 10.1, P = 0.004), and 12.5:1 (20.1 ± 10.9 versus 12.3 ± 7.5, P = 0.011). In RPL group, peripheral blood NK cell levels (%) showed a significant positive correlation with NK cell cytolytic activities at E/T ratio of 50:1 (r = 0.522, P < 0.001), 25:1 (r = 0.588, P < 0.001), and 12.5:1 (r = 0.604, P < 0.001). In controls, CD3(+)/8(+) cells (%) show a negative correlation with NK cell cytolytic activities at E/T ratio of 50:1 (r = -0.566, P = 0.028), 25:1 (r = -0.60., P = 0.017), and 12.5:1 (r = -0.602, P = 0.018). Ratios of T-helper cell to T-cytotoxic cell are positively correlated with NK cell cytolytic activities at E/T ratio of 50:1 (r = 0.601, P = 0.018), 25:1 (r = 0.632, P = 0.012), and 12.5:1 (r = 0.637, P = 0.011). 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.