Innate immunity in pregnancy

Abstract

In a previous Comment1xPaternal leukocytes selectively increase secretion of IL-4 in peripheral blood during normal pregnancies (demonstrated by a novel one-way MLC measuring cytokine secretion) . Ekerfelt, C. et al. Am. J. Reprod. Immunol. 1997; 38: 320–326Crossref | PubMedSee all References, Ekerfelt et al. make an important point that the maternal immune system as a whole is likely to be modulated in several ways during the course of pregnancy. For too long we have expected to solve the great problem of how the fetus avoids maternal immune rejection without compromising its host by focusing on a single mechanism. But whether it is trophoblast expression of HLA-G, the suppression of natural killer cell activity, or a maternal T helper 2 (Th2) response bias, it is apparent that numerous adaptations could operate in parallel. The work by Ekerfelt et al. provides more evidence that pregnancy is associated with a certain degree of Th2 response bias1xPaternal leukocytes selectively increase secretion of IL-4 in peripheral blood during normal pregnancies (demonstrated by a novel one-way MLC measuring cytokine secretion) . Ekerfelt, C. et al. Am. J. Reprod. Immunol. 1997; 38: 320–326Crossref | PubMedSee all References, although it is still uncertain whether this is a generalized phenomenon or specific for fetal antigens. Indeed, in broad agreement, we have found that maternal peripheral blood lymphocytes have suppressed Th1 responses to mitogenic stimuli.Our Viewpoint article on innate function in pregnancy does not disagree with current concepts of T-cell function in pregnancy2xAn innate view of human pregnancy. Sacks, G. et al. Immunol. Today. 1999; 20: 114–118Abstract | Full Text | Full Text PDF | PubMed | Scopus (317)See all References. However, it is an attempt to redirect some research emphasis away from specific immunity and towards innate immunity. It is of considerable interest that many components of innate immunity (including monocytes) are in an activated state in pregnancy. On the one hand it is intriguing how and why this occurs, and on the other hand, innate activation provides another powerful mechanism to modulate maternal specific immune responses. Innate immunity has a critical regulatory role on any immune response3xThe instructive role of innate immunity in the acquired immune response. Fearon, D. and Locksley, R. Science. 1996; 272: 50–53Crossref | PubMedSee all References. Thus in trying to understand the function of T cells in pregnancy, it is essential that we also explore the nature of ′costimulation (or ′signal P′2) provided by innate activation. This may be in the form of monocyte surface antigen expression4xNormal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Sacks, G. et al. Am. J. Obstet. Gynecol. 1998; 179: 80–86Abstract | Full Text | Full Text PDF | PubMed | Scopus (530)See all References, monocyte cytokine production (we have found that monocytes from pregnant women are primed to produce interleukin 12 but not tumour necrosis factor a), or other metabolic effects5xPrevention of allogeneic fetal rejection by tryptophan catabolism. Munn, D. et al. Science. 1998; 281: 1191–1193Crossref | PubMedSee all References. During pregnancy, components of maternal specific immunity are likely to be influenced not just by placental products but also by activated innate immunity. This may explain the unique immunological function of pregnant women.