Changes in systemic type 1 and type 2 immunity in normal pregnancy and pre-eclampsia may be mediated by natural killer cells

A bias of T cell immunity towards type 2 (Th2) is thought to be critical for normal pregnancy. Pathological pregnancies, such as pre-eclampsia, are characterised by cell-mediated (Th1) immune dominance. The Th1/Th2 paradigm, however, is too simplistic. Normal pregnancy is associated with a systemic inflammatory response which increases throughout gestation. This inflammatory response is exaggerated in pre-eclampsia, a syndrome of the third trimester. T helper (Th) cells are considered the primary mediators of these altered immune responses, and other T cells, i.e. T cytotoxic (Tc) cells, and lymphocytes of the innate immune system, i.e. natural killer (NK) and NKT cells, have been largely disregarded. In this study, we have used novel pan type 1 (IL-18 receptor) and pan type 2 (ST2L) lymphocyte function markers in four-colour flow cytometry to broadly characterise peripheral blood lymphocyte populations from non-pregnant, normal pregnant and pre-eclamptic women. There were no changes in the Th1/Th2 or Tc1/Tc2 cell ratios between the three groups; however, the NK1/NK2 and NKT1/NKT2 cell ratios were significantly decreased in normal pregnancy compared with non-pregnant (p <0.001 and p <0.01, respectively) and pre-eclamptic women (p <0.05). These results confirm that immunoregulation occurs in pregnancy, but suggest a dominant role of the innate rather than the adaptive immune system.