Interleukin-10 is produced by human uterine natural killer cells but does not affect their production of interferon-γ

Abstract

A predominance of T helper (Th)2-type cytokines and a weakening of Th1 responses seem to be critical for the maintenance of a successful gestation. Among Th2-type cytokines, interleukin (IL)-10 is produced by human cytotrophoblasts and defects in this production result in specific pathological conditions of pregnancy. The current opinion is that IL-10 serves to protect the fetus from a harmful maternal immune response. However, production of the cytokine and its direct effect on uterine natural killer (uNK) cells, which represent the predominant lymphocyte population infiltrating the pregnant endometrium, are largely unknown. Thus, to shed light on the cytokine network at the maternal-fetal barrier during early pregnancy, we investigated the IL-10 system in uNK cells. We showed that uNK cells express the mRNA transcripts for IL-10 and IL-10 receptor. Production of IL-10 by the uNK cells was enhanced by both IL-2 and IL-12. Treatment with IL-10 alone enhanced uNK cell cytotoxic activity. In contrast, the cytokine did not modify the basal or stimulated production of interferon (IFN)-γ by uNK. Thus, IL-10 does not act as a direct antagonist of uNK cell function and activation. However, IL-10 produced by uNK cells in response to IL-12 and IL-2 may still have a feedback inhibitory effect on the production of deleterious cytokines within the uterine microenvironment.