Immunomodulatory Effects of Human Amniotic Epithelial Cells on Naive Cd4+ T Cells From Women With Unexplained Recurrent Spontaneous Abortion Publisher Pubmed



Motedayyen H^{1, 2} ; Zarnani AH^{3, 4} ; Tajik N^{5, 6} ; Ghotloo S⁷ ; Rezaei A² Show Affiliations
Source: Placenta Published:2018

Abstract

Introduction: Immune imbalance at the maternal-fetal interface plays a fundamental role in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). Human amniotic epithelial cells (hAECs) possess pregnancy-friendly immunomodulatory effects. Here, we investigated how function of naive CD4+ T cells from URSA patients is affected by hAECs. Methods: Phenotypic characteristics of hAECs were determined by flow cytometry and their effect on proliferation of allogeneic peripheral blood mononuclear cells (PBMCs) was evaluated by a BrdU cell proliferation assay. Naive CD4+ T cells were isolated from 25 URSA patients and 5 healthy women and co-cultured with hAECs. Immunomodulatory effects of hAECs on cytokines profile, proliferation of stimulated CD4+ T cells and induction of regulatory T cells (Tregs) were assessed by ELISA and flow cytometry, respectively. Functional competency of Tregs was evaluated in an allogeneic mixed lymphocyte reaction (MLR) system. Results: hAECs did not elicit allogeneic proliferative responses of PBMCs, inhibited proliferation of naive CD4+ T cells, induced production of Th2 and suppressed production of Th1 and Th17 cytokines. hAECs showed the ability to induce differentiation of Tregs and production of transforming growth factor-beta1 (TGF-β1) and interleukin-10 (IL-10). This ability was found to be superior in control subjects compared to URSA patients. Indeed, Tregs generated in the presence of hAECs expressed higher levels of CTLA-4 compared to Tregs generated in their absence and restrained the proliferation of autologus PBMCs in MLR system. Conclusion: Based on these findings, hAECs can be considered as one potential candidate in immunotherapy of patients with URSA. © 2018