Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10

J Exp Med. 1996 Aug 1;184(2):539-48. doi: 10.1084/jem.184.2.539.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • DNA Primers / chemistry
  • Gene Expression
  • Humans
  • Immune Tolerance*
  • Interferon-gamma / metabolism
  • Interleukin-10 / biosynthesis*
  • Lymphocyte Culture Test, Mixed
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Trophoblasts / cytology
  • Trophoblasts / immunology*
  • Trophoblasts / metabolism


  • DNA Primers
  • RNA, Messenger
  • Interleukin-10
  • Interferon-gamma