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Abstract:

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. © The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Registro:

Documento: Artículo
Título:A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation
Autor:Fraccaroli, L.; Alfieri, J.; Larocca, L.; Calafat, M.; Mor, G.; Leirós, C.P.; Ramhorst, R.
Filiación:Laboratory of Immunopharmacology, School of Sciences, University of Buenos Aires, Int. Guiraldes 2160, C1428EHA Buenos Aires, Argentina
Department of Obstetrics and Gynaecology, School of Medicine, Yale University, United States
Laboratory of Immunogenetics, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
Palabras clave:Chemokines; Recurrent spontaneous miscarriages; T cell; Tolerance and pregnancy; CD4 antigen; chemokine; gamma interferon; interleukin 12p70; leukemia inhibitory factor; lipocortin 5; nitrite; progesterone; RANTES; transcription factor FOXP3; tumor necrosis factor alpha; apoptosis; article; CD3+ T lymphocyte; CD4+ CD25+ Foxp3+ T lymphocyte; cell death; cell proliferation; cell selection; cell strain Swan 7I; cell survival; clinical article; coculture; enzyme linked immunosorbent assay; female; fluorescence activated cell sorting; human; human cell; immune response; kinetics; leukemia; leukocyte; peripheral blood mononuclear cell; regulatory T lymphocyte; spontaneous abortion; T lymphocyte activation; trophoblast; Western blotting
Año:2009
Volumen:24
Número:1
Página de inicio:166
Página de fin:175
DOI: http://dx.doi.org/10.1093/humrep/den344
Título revista:Human Reproduction
Título revista abreviado:Hum. Reprod.
ISSN:02681161
CODEN:HUREE
CAS:gamma interferon, 82115-62-6; lipocortin 5, 111237-10-6; nitrite, 14797-65-0; progesterone, 57-83-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02681161_v24_n1_p166_Fraccaroli

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Citas:

---------- APA ----------
Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Mor, G., Leirós, C.P. & Ramhorst, R. (2009) . A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation. Human Reproduction, 24(1), 166-175.
http://dx.doi.org/10.1093/humrep/den344
---------- CHICAGO ----------
Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Mor, G., Leirós, C.P., et al. "A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation" . Human Reproduction 24, no. 1 (2009) : 166-175.
http://dx.doi.org/10.1093/humrep/den344
---------- MLA ----------
Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Mor, G., Leirós, C.P., et al. "A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation" . Human Reproduction, vol. 24, no. 1, 2009, pp. 166-175.
http://dx.doi.org/10.1093/humrep/den344
---------- VANCOUVER ----------
Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Mor, G., Leirós, C.P., et al. A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation. Hum. Reprod. 2009;24(1):166-175.
http://dx.doi.org/10.1093/humrep/den344