Granulated metrial gland cells: A natural killer cell subset of the pregnant murine uterus

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Abstract
The metrial gland develops in the uterus of many rodent species during normal pregnancy. It is a maternally‐derived tissue that contains stromal and vascular elements plus a population of large cells, striking in their light microscopic appearance due to the presence of numerous cytoplasmic granules. These cells, which have become known in mice and rats as granulated metrial gland (GMG) cells, are derived from bone marrow precursors and recent work suggests they are a subset of lymphocytes belonging to the natural killer (NK) cell lineage. The functions of GMG cells during normal gestation have not been clearly defined. In vitro, GMG cells have been shown to produce cytokines and their cytokine profile is altered upon addition of medium containing the T cell growth factor interleukin‐2 (IL‐2). GMG cell granules contain the cytolytic protein perforin but GMG cells have a very limited capacity to kill in vitro unless they have been stimulated by IL‐2 or interferon‐gamma. Histological study of GMG cells has suggested they preferentially associate with fetal trophoblast. Since trophoblast appears resistant to immune lysis, except by IL‐2‐activated effector lymphocytes, and because resorbing murine embryos become infiltrated by lytic cells of the NK cell lineage, it is important to establish whether GMG cells are activated by pregnancy‐associated events to play a major lytic role in vivo.