title: Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10.
abstract: The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus.
authors: Department of Anatomy, University of California San Francisco 94143, USA.
authors: I
authors: I
authors: Roth
authors: D B
authors: DB
authors: Corry
authors: R M
authors: RM
authors: Locksley
authors: J S
authors: JS
authors: Abrams
authors: M J
authors: MJ
authors: Litton
authors: S J
authors: SJ
authors: Fisher
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D007959:Lymphocyte Culture Test, Mixed; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma