Immunological aspects of implantation and implantation failure

The human endometrium contains a significant proportion of leukocytes (8-35 % of all cells), the absolute numbers and proportions varying during both t he menstrual cycle and early in pregnancy. T cells, macrophages and a popul ation of phenotypically unusual large granular lymphocytes (LGL) are common ly present, although B cells are absent. Relative T cell numbers decrease s ignificantly in first trimester decidua, and hence are unlikely to play an important role in maintenance of human pregnancy, but T cells could be impo rtant in implantation where their relative numbers are greater. In addition to producing cytokines, local tissue macrophages may provide an immediate antigen non-specific host defence to infection. Most attention has, neverth eless, focused on a role for LGL in implantation and maintenance of pregnan cy since, at the time of implantation, LGL comprise 70-80% of the total end ometrial leukocyte population. Although endometrial LGL have been shown to express natural killer (NK) cell-type cytotoxicity against classical NK cel l targets, such cytotoxicity against trophoblast is induced only after acti vation by interleukin (IL)-2. Selective expression of the unusual class I h uman leukocyte antigen (HLA) molecule, KLA-G, by extravillous cytotrophobla st may assist in protecting invasive cytotrophoblast from potential materna l NK cell attack, probably via interactions with killer inhibitory receptor molecules on LGL. Many cytokines have been demonstrated to be expressed at the maternal-fetal interface although, currently, in mice only two (IL-11 and leukaemia inhibitory factor) appear to be absolutely essential for succ essful pregnancy outcome. Immune effector cells and cytokines may also play a role in human pregnancy pathologies, such as recurrent early pregnancy l oss.