Suppression of natural killer cell cytotoxicity in postpartum women: time course and potential mechanisms

Abstract

Little is known about the recovery of the immune system from normal pregnancy and whether the postpartum period is a uniquely adapted immune state. This report extends previous observations from our group of decreased natural killer (NK) cell cytotoxicity in the postpartum period. NK cytotoxicity was measured from 1 week through 9 months postpartum. In addition, NK cytotoxicity was assayed in the presence or absence of pooled plasmas collected from either postpartum or nonpostpartum women. Samples of cells were stained for inhibitory receptors and analyzed by flow cytometry. NK cytotoxicity remained decreased in postpartum women compared to controls through the first 6 postpartum months, returned to normal levels by 9 months, and remained normal at 12 months. NK cytotoxicity during the first 6 months was further inhibited by the addition of pooled plasma to NK cultures from postpartum women, but the addition of pooled plasma from the control group did not affect that group's NK cultures. There were differences in inhibitory receptor staining between the two groups, with decreased CD158a and CD158b and increased NKG2A expression on postpartum NK cells during the first 3 postpartum months. These data suggest that NK cytotoxicity postpartum inhibition lasts 6 months and is influenced by unidentified postpartum plasma components. The effect may also involve receptors on NK cells.

Keywords: NK cytotoxicity; flow cytometry; human leukocyte antigen-G; plasma effects; postpartum inhibition.

Figure 1

Natural killer (NK) cell cytotoxicity (measured in lytic units) in women across postpartum months compared to controls. Bars represent means, and error bars are standard errors of the mean. NK cell cytotoxicity was significantly lower in postpartum women than in controls through 6 months postpartum. *p = .05. **p = .01. ***p = .001. The difference between groups was nonsignificant (NS) at 9 months and at 12 months (data not shown).

Figure 2

Natural killer (NK) cell cytotoxicity at 50:1 effector:target (E:T) ratio in postpartum NK assays (n = 34) with and without the addition of pooled postpartum plasma. Error bars are standard errors of the means.

Figure 3

Soluble human leukocyte antigen (sHLA)-G staining across the postpartum period.

Figure 4

Inhibitory-receptor staining of postpartum natural killer (NK) cells (n = 31) compared to cells from age-matched nonpostpartum controls (n = 10). Error bars represent standard errors of the means. CD158a and CD158b were significantly lower (p = .001 and .017, respectively), and NKG2A significantly higher in postpartum compared to controls (p = .03.