Table 3.

Changes in systemic innate lymphoid cells during normal pregnancy.

Component	Main findings	References
NK cells
	No change in total numbers or frequency of NK subsets (CD56dim, CD56bright), iNKT and NKT cells in peripheral blood between non-pregnant and pregnant women, regardless of the trimester of pregnancy.	135–137
	Reduction in NK cell numbers in pregnant vs. non-pregnant women	138, 139
	Decreased ratio of type 1 NK cells (defined as expressing IL18R1) to type 2 NK cells (defined as expressing IL1RL1) in the third trimester compared to healthy controls.	140
	Lower percentage of IL18R1 expressing NK cells in the third trimester compared to non-pregnant controls. Reduced number of IL18R1 surface molecules per NK cells.	140
	Increased homing receptor expression on type 2 CD56bright NK cells in the second trimester, compared to the first and third trimester.	135
	Increased expression of surface-marker immune checkpoint protein TIM-3 on NK cells and monocytes in pregnancy.	137, 141
	Elevated plasma levels of Galectin-9 (TIM-3 ligand) throughout all trimesters of pregnancy.	137
	Increase in expression of the activation marker CD69 on CD4neg iNKT cells from the first to the third trimester, although the levels are not significantly different to age-matched non-pregnant controls.	136
	Increased expression of the degranulation marker LAMP-1 (CD107a) on CD56dim cells after PMA-ionomycin stimulation and baseline levels of the natural cytotoxicity receptor NKp46 (CD335) in the third trimester as compared to non-pregnant women.	101, 137
	Reduced IFN-γ production and increased IL-10 production upon ex vivo stimulation with PMA-ionomycin by NK cells from the first trimester compared to non-pregnant women.	142

NK, Natural killer; iNKT, Invariant natural killer T; NKT, natural killer T; TIM-3, T-cell immunoglobulin- and mucin domain-containing-3; LAMP-1, lysosome-associated membrane protein-1; PMA, phorbol-12-myristate-13-acetate, IFN-γ. Interferon – γ.