title: Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells.
abstract: 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.
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires and National Research Council (CONICET), Argentina.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ramhorst
authors.forename: Laura
authors.initials: L
authors.lastname: Fraccaroli
authors.forename: Paulomi
authors.initials: P
authors.lastname: Aldo
authors.forename: Ayesha B
authors.initials: AB
authors.lastname: Alvero
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cardenas
authors.forename: Claudia Perez
authors.initials: CP
authors.lastname: Leirós
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
mesh_terms: D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D017077:Culture Media, Conditioned; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D016212:Transforming Growth Factor beta