CONICET | Buscador de Institutos y Recursos Humanos

Problem The specialized regulatory T cells (Treg) population, essential for maternal tolerance of the conceptus, 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 differentiation, recruit these cells, 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 fertile women PBMCs 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. As a control, a lower TGF producer ovarian cancer cell line (OVC1) was used. Co-culture experiments were done 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 Swan-71 and HTR8 constitutively secrete high levels of TGF and induced a significant increase of Foxp3 expression accompanied by a specific T-reg cytokine profile. Moreover, both cell lines were able to recruit iTregs in a specific-manner, tested by transwells assays that correlated with a specific chemokine profile. However, OVC1 SFCM neither induced Foxp3 expression nor recruited iTregs. Finally, in transwells assays using differentiated iTregs and Swan-71 cells, Swan-71 cells could selectively recruit Foxp3+ cells, which were significantly increased in the presence of the mentioned stimuli. Conclusion Altogether, these data suggest that trophoblast cells might contribute to the local differentiation of iTregs, and to their recruitment towards the placental-maternal interface.