Implication of RANTES in the modulation of alloimmune response by progesterone during pregnancy

Abstract

Problem: Several studies indicate that RANTES (regulated on activation, normal T cell expressed and secreted) is able to downregulate T-cell responses which suggest it might be relevant for fetal tolerance induction. However, the role of RANTES in pregnancy had not been established. Here we investigate RANTES regulation during early pregnancy and potential failures leading to losses of pregnancies. Method of study: RANTES and progesterone levels were determined in sera and feto-placental units from high resorption rate CBA/J × DBA/2 pregnant females and compared with CBA/J × BALB/c normal pregnant mice. RANTES in vitro modulation was also studied in nulliparous, primiparous and multiparous CBA/J and BALB/c cells in response to paternal alloantigen and progesterone stimulation. Results: Nulliparous CBA/J females were quantitatively deficient in RANTES sera levels, whereas pregnancies with male BALB/c or DBA/2 increased its production. However, feto-placental units from CBA/J females are high producers of progesterone and RANTES. Conclusion: These data suggest that the beneficial effect of RANTES on feto-maternal interface requires an optimal concentration range and might be modulated by progesterone, hence exacerbated placental expression could be associated with high resorption rate.