Induction of Maternal Tolerance to Fetal Alloantigens by RANTES Production

Am J Reprod Immunol. Nov-Dec 2006;56(5-6):302-11. doi: 10.1111/j.1600-0897.2006.00430.x.


Problem: Previous studies have demonstrated a requirement for RANTES (regulated on activated normal T-cell expressed, and secreted) at immune privileged sites; we have investigated the role of RANTES in the induction of maternal-fetal tolerance.

Method of study: Endometrial and peripheral T lymphocytes were obtained from women with recurrent pregnancy losses (RPLs) and fertile women. RANTES modulation by progesterone or paternal alloantigens was measured by enzyme-linked immunosorbent assay or flow cytometry analysis.

Results: Progesterone significantly increased intracellular RANTES expression in CD4+ and CD8+ endometrial T cells. Moreover, alloreactive lymphocytes from RPL patients produced lower RANTES levels when compared with those from fertile women. At the local level, treatment with recombinant RANTES induced a decrease in CCR5 and CXCR4 messenger RNA that correlated with an increase in T-bet expression. RPL patients and normally fertile women express RANTES similarly, but differ in their patterns of RANTES receptor expression.

Conclusion: RANTES may be implicated in the local induction of a Th1-type response necessary for successful implantation. Altered response to RANTES stimulation among some RPL patients may be responsible for poor pregnancy outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / immunology
  • Biomarkers
  • Chemokine CCL5 / biosynthesis*
  • Embryo Transfer
  • Endometrium / immunology
  • Endometrium / metabolism
  • Female
  • Fertility
  • Fetus / immunology*
  • Fetus / metabolism*
  • Humans
  • Immune Tolerance / immunology*
  • Isoantigens / immunology*
  • Mothers
  • Progesterone / metabolism
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism


  • Biomarkers
  • Chemokine CCL5
  • Isoantigens
  • Progesterone