Induction of maternal tolerance to fetal alloantigens by RANTES production.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Ramhorst
Rosanna
R
Division of Immunogenetics and Gynecology, University of Buenos Aires, Buenos Aires, Argentina.
Patel
Rahdika
R
Corigliano
Adriana
A
Etchepareborda
Juan José
JJ
Fainboim
Leonardo
L
Schust
Danny
D
D000026:Abortion, Habitual / Q000276:immunology; D015415:Biomarkers; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004624:Embryo Transfer; D004717:Endometrium / Q000276:immunology / Q000378:metabolism; D005260:Female; D005298:Fertility; D005333:Fetus / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D009035:Mothers; D011374:Progesterone / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D015415:Biomarkers; D018946:Chemokine CCL5; D007519:Isoantigens; D011374:Progesterone