INDUCTION AND RECRUITMENT OF REGULATORY T CELLS BY TROPHOBLAST CELLS: RELEVANCE OF THE NEUROPEPTIDE VIP

LAURA FRACCAROLI; ESTEBAN GRASSO; VANESA HAUK; GIL MOR; CLAUDIA PÉREZ LEIRÓS; ROSANNA RAMHORST

Hamburgo

Congreso; Joint International Congress ASRI-ESRI 2012; 2012

PROBLEM: Pregnancy involves different stages characterized by an initial pro-inflammatory response, crucial for implantation and placentation, that must be finely controlled by several regulatory and tolerogenic mechanisms for growth and development of the embryo. In particular, the specialized regulatory T cell (Treg) population is essential for maternal tolerance exerting their suppressive functions in the critical peri implantation phase of pregnancy. Moreover, the role of neuropeptides in maternal-fetal tolerance is becoming a topic of growing interest. Particularly, our focus is on the vasoactive intestinal peptide (VIP) which modulates the immune response towards a tolerogenic profile and we have recently shown that VIP is synthesized and secreted by first trimester human trophoblast cells (Swan-71). The aim of this work is to evaluate the contribution of VIP to the differentiation and recruitment of iTreg cells toward the maternal-placental interface. METHOD: Fertile women PBMC and Swan-71 cell line were co-cultured in the absence or presence of VIP (10-7M) 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. Swan-71 cells co-cultured or not with PBMC in a transwell system were recovered and chemokines expression was assessed by FACS and PCR analysis. RESULTS: VIP (10-7M) significantly increased the frequency of CD4+CD25+Foxp3+ cells in PBMC after the co-culture with trophoblast cells; this effect was prevented by VIP antagonist (P