Leucocyte populations and cytokine regulation in human uteroplacental tissues

Abstract

Human endometrial tissue and the decidualized endometrium in pregnancy contain relatively large numbers of leucocytes, the proportions of which vary during both the menstrual cycle and early pregnancy. CD3+ T-cells, CD14+ macrophages and a population of phenotypically unusual CD3-CD16-CD56++ large granular lymphocytes (LGL) are present, whereas B-cells are virtually absent. Relative T-cell numbers decrease in first-trimester decidua; T-cells are therefore unlikely to have an important role in the immunological maintenance of pregnancy but could be more important in implantation, when their relative numbers are greater. Extensive numbers of class II MHC-positive tissue macrophages in both the endometrium and placenta will provide an immediate antigen non-specific host defence to infection at this important site. Nevertheless, most attention has focused on a role for the predominant LGL endometrial cell population in the implantation and maintenance of pregnancy because, at the time of implantation, these LGLs comprise 70-80% of all leucocytes in the endometrium. It is now well recognized that there is substantial and complex cytokine activity within human uteroplacental tissues; both leucocytic and non-leucocytic cells have been shown to be capable of producing a significant array of cytokines. However, to avoid excessive pathological sequelae, such cytokine activity must be locally regulated. This has been highlighted by recent reports indicating that abnormal Th1-type cytokine responses could be a reason for immunological reproductive failure in women. Key cytokines controlling differentiation into a Thl (interleukin 12) or Th2 (interleukin 4) type pattern both exist in unusual molecular forms at the human maternal-fetal tissue interface and hence might be fundamental regulatory elements controlling cytokine action locally by an antagonistic action.