Modulation and Recruitment of Inducible Regulatory T Cells by

RAMHORST R; FRACCAROLI L; ALDO P; ALVERO AB; CARDENAS I; PEREZ LEIROS C; MOR G

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; 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 naý¨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.