Academic Journal
A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation
العنوان: | A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation |
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المؤلفون: | Fraccaroli, Laura, Alfieri, Julio, Larocca, Luciana, Calafat, Mario, Mor, Gil, Leirós, Claudia Pérez, Ramhorst, Rosanna |
بيانات النشر: | Oxford University Press |
سنة النشر: | 2009 |
المجموعة: | HighWire Press (Stanford University) |
مصطلحات موضوعية: | Reproductive biology |
الوصف: | BACKGROUND Successful implantation is followed by a local pro-inflammatory and Th1 response, subsequently controlled by Th2. Regulated upon activation, normal T cell expressed and secreted (RANTES) promotes a Th1 response and is implicated as a physiologic tolerogenic factor; therefore, we studied its potential role in the trophoblast–maternal leukocyte dialog. METHODS We performed co-cultures of immortalized trophoblast cell line (Swan 71) and peripheral blood mononuclear cells (PBMCs) from fertile women ( n = 23) or with recurrent spontaneous abortions ( n = 18, RSA). After 24 and 48 h, supernatant and cells were analyzed by enzyme-linked immunosorbent assay, fluorescence-activated cell sorting, Western blot and apoptosis assay. To investigate the physiological effects at peripheral level, we co-cultured maternal and paternal PBMCs with conditioned media from Swan cells and progesterone. RESULTS Following interaction of maternal PBMCs and trophoblast cells, RANTES production increased ( P < 0.05) and was accompanied by low levels of interferon γ, interleukin-12 p70 and high levels of tumor necrosis factor-α, nitrites and leukemia-inhibitory factor. RANTES production resulted in elevated apoptosis of potentially deleterious maternal CD3+ lymphocytes, accompanied by a decrease in the proliferative maternal response. During fetal–maternal dialog, the anti-RANTES antibody significantly reduced the frequency of CD4+CD25+Foxp3+ cells ( P < 0.05) and was associated with trophoblast cell survival. However, co-cultures of Swan cells and RSA-PBMCs displayed a differential RANTES kinetics, lower levels of regulatory T cells (Tregs) and CD3+annexin-V+cells, accompanied by higher levels of apoptotic trophoblast cells. CONCLUSIONS RANTES promotes an adequate pro-implantatory microenvironment that influences trophoblast cell survival and modulates the balance of maternal Treg/T effector lymphocytes in favor of maternal tolerance. |
نوع الوثيقة: | text |
وصف الملف: | text/html |
اللغة: | English |
Relation: | http://humrep.oxfordjournals.org/cgi/content/short/24/1/166; http://dx.doi.org/10.1093/humrep/den344 |
DOI: | 10.1093/humrep/den344 |
الاتاحة: | http://humrep.oxfordjournals.org/cgi/content/short/24/1/166 https://doi.org/10.1093/humrep/den344 |
Rights: | Copyright (C) 2009, European Society of Human Reproduction and Embryology |
رقم الانضمام: | edsbas.77886524 |
قاعدة البيانات: | BASE |
DOI: | 10.1093/humrep/den344 |
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