Paternal leukocytes selectively increase secretion of IL-4 in peripheral blood during normal pregnancies: demonstrated by a novel one-way MLC measuring cytokine secretion.

PROBLEM

It has been proposed that immune responses in normal pregnancy are Th2-like, thereby protecting the fetus and placenta from being rejected. Some studies have shown Th2-deviated systemic responses to different antigens and mitogens. The aim of this study was to demonstrate the specific T cell cytokine responses directed toward paternal histocompatibility leukocyte antigen (HLA), because this is the most prominent target for rejection of the feto-placental unit.

METHOD OF STUDY

A novel one-way mixed leukocyte culture (MLC) combined with the detection of cytokine secretion with a sensitive ELISPOT assay was developed. Peripheral blood from 11 pregnant women was investigated with respect to allo-reactivity toward paternal leukocytes and pooled leukocytes from unrelated blood donors. This was done at three different occasions during pregnancy and 8 weeks after delivery. Nine age-matched non-pregnant women served as controls.

RESULTS

In the second and third trimesters of pregnancy significantly larger numbers of IL-4-secreting cells (Th2) were induced by paternal leukocytes as compared to unrelated leukocytes.

CONCLUSIONS

The findings indicate a selective immune deviation toward Th2, which may protect the fetus from rejection and thus may be an important homeostatic mechanism in normal pregnancies.