Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10

Iris Roth, David B. Corry, Richard M. Locksley, John S. Abrams, Mark J. Litton, Susan J. Fisher

Research output: Contribution to journalArticlepeer-review

307 Scopus citations

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/106 cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped ~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 γ 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.

Original languageEnglish (US)
Pages (from-to)539-548
Number of pages10
JournalJournal of Experimental Medicine
Volume184
Issue number2
DOIs
StatePublished - Aug 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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