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Modulation and Recruitment of Inducible Regulatory T Cells by First Trimester Trophoblast Cells

Authors


Gil Mor, Department of Obstetrics and Gynecology, School of Medicine, Yale University, 333 Cedar St. PO Box 208063, New Haven, CT 06520, USA.
E-mail: gil.mor@yale.edu

Abstract

Citation Ramhorst R, Fraccaroli L, Aldo P, Alvero AB, Cardenas I, Leirós CP, Mor G. Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells. Am J Reprod Immunol 2012; 67: 17–27

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 naïve CD45RA+ CCR7+ cells obtained from peripheral blood mononuclear cells cultured with IL-2 and TGFβ 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 TGFβ 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.

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