Induction of maternal tolerance to fetal alloantigens by RANTES production

R. RAMHORST, R. PATEL, A. CORIGLIANO, J.J. ETCHEPAREBORDA, L. FAINBOIM AND D. SCHUST.

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2006 vol. 56 p. 302 - 311

1046-7408

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> 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.