Hossein Motedayyen1, Amir-Hassan Zarnani2, Nader Tajik3, Somayeh Ghotloo4, Abbas Rezaei5. 1. Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: hm.k_65@yahoo.com. 2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. 3. Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran; Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 4. Department of Laboratory Medicine, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran. 5. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: Rezaei@mui.ac.ir.
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.
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.
Authors: Hossein Motedayyen; Farshid Fathi; Mahdi Fasihi-Ramandi; Ali Mohammad Sabzghabaee; Ramezan Ali Taheri Journal: J Res Med Sci Date: 2019-01-31 Impact factor: 1.852