VIP-contribution to the induction and recruitment of regulatory T cells in an in vitro model of maternal-placental interaction

L. FRACCAROLI; E. GRASSO; V. HAUK; G. MOR; C. PÉREZ LEIRÓS; R. RAMHORST

Buenos Aires

Simposio; 3rd Latin American Symposium of Reproductive Immunology and 1st. Latin American Satellite Symposium American Society of Reproductive Immunology; 2011

American Society of Reproductive Immunology

Introduction During pregnancy, regulatory T cells (Treg) are crucial to control the pro-inflammatory immune response. Vasoactive intestinal peptide (VIP) modulates the immune response to a tolerogenic profile and we have recently shown that VIP is synthesized and secreted by trophoblast cells. The aim of this work is to evaluate the contribution of VIP in the differentiation and recruitment of iTreg cells toward the maternal-placental interface. Materials and Methods Fertile women PBMC and trophoblast cells (Swan-71 cell line) were co-cultured and iTreg frequency and cytokines expression were measured by FACS analysis after 48h. Co-cultured PBMCs were used for suppression assays and T cell proliferation was measured by 3H-thymidine incorporation. Migration assays were performed to evaluate recruitment of differentiated iTreg cells towards Swan-71. Results VIP (10-7M) significatively increased the frequency of CD4+CD25+Foxp3+ cells in co-cultures, this effect was prevented by its antagonist (P<0.05). Moreover, these cells suppressed the proliferation of alloactivated lymphocytes. VIP increased the % of CD4+IL10+ cells (1.9±0.2 vs. 25±3, P<0.05) in the co-culture but it did not modulate the production of IFNg and IL-17. To evaluate the mechanisms involved in the induction of iTreg in this model and taking into account Swan cells produce high levels of TGFb1/2, we performed transwell assays. We observed that the increase in CD4+CD25+Foxp3+ frequency was prevented in the presence of anti-TGFb neutralizing antibody and VIP antagonist. Finally, Swan-71 cells selectively recruited iTregs and this effect was higher in the presence of VIP. Conclusion VIP could have an active role in the immunoregulatory processes operating in the maternal-placental interface by contributing to the induction and recruitment of iTregs.