Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells

R. RAMHORST; L. FRACCAROLI; P. ALDO; A. ALVERO; I. CARDENAS; C. PÉREZ LEIRÓS; G. MOR

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2012 vol. 67 p. 17 - 27

1046-7408

Problem The specialized regulatory T-cells (Treg) population, essential for maternal tolerance of the fetus, performs its suppressive actions in the critical peri-implantation phase of pregnancy. In the present work, we investigated whether trophoblast cells are able to induce Treg recruitment, differentiation, and whether these mechanisms are modified by a bacterial or viral infection. Method of Study Human T-regulatory cells were differentiated from naı¨ve CD45RA+CCR7+cells obtained from peripheral blood mononuclear cells cultured with IL-2 and TGFb over 5 days. Induction of iTregs (CD4+Foxp3+ cells)was evaluated using low serum conditioned media (LSCM), obtained from two first trimester trophoblast cell lines, Swan-71 and HTR8. Coculture experiments were carried out using transwell assays where trophoblast cells were in the absence or presence of PGN, LPS, or Poly [I:C]. Cytokine production was measured by multiplex analysis. Results Trophoblast cells constitutively secrete high levels of TGFb and induced a significant increase of Foxp3 expression accompanied by a specific T-reg cytokine profile. Moreover, trophoblast cells were able to recruit iTregs in a specific manner. Conclusion We demonstrate that trophoblast cells have an active role on the recruitment and differentiation of iTregs, therefore, contributing to the process of immune regulation at the placental–maternal interface.