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Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells

Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to exert immunomodulatory effects on naive and memory CD4(+) T cells...

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Autores principales: Maggi, Jaxaira, Schinnerling, Katina, Pesce, Bárbara, Hilkens, Catharien M., Catalán, Diego, Aguillón, Juan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027201/
https://www.ncbi.nlm.nih.gov/pubmed/27698654
http://dx.doi.org/10.3389/fimmu.2016.00359
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author Maggi, Jaxaira
Schinnerling, Katina
Pesce, Bárbara
Hilkens, Catharien M.
Catalán, Diego
Aguillón, Juan C.
author_facet Maggi, Jaxaira
Schinnerling, Katina
Pesce, Bárbara
Hilkens, Catharien M.
Catalán, Diego
Aguillón, Juan C.
author_sort Maggi, Jaxaira
collection PubMed
description Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to exert immunomodulatory effects on naive and memory CD4(+) T cells in an antigen-specific manner. For this purpose, MPLA-tDCs were loaded with purified protein derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4(+) T cells. Lymphocytes were re-challenged with autologous PPD-pulsed mature DCs (mDCs), evaluating proliferation and cytokine production by flow cytometry. On primed-naive CD4(+) T cells, the expression of regulatory T cell markers was evaluated and their suppressive ability was assessed in autologous co-cultures with CD4(+) effector T cells and PPD-pulsed mDCs. We detected that memory CD4(+) T cells primed by MPLA-tDCs presented reduced proliferation and proinflammatory cytokine expression in response to PPD and were refractory to subsequent stimulation. Naive CD4(+) T cells were instructed by MPLA-tDCs to be hyporesponsive to antigen-specific restimulation and to suppress the induction of T helper cell type 1 and 17 responses. In conclusion, MPLA-tDCs are able to modulate antigen-specific responses of both naive and memory CD4(+) T cells and might be a promising strategy to “turn off” self-reactive CD4(+) effector T cells in autoimmunity.
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spelling pubmed-50272012016-10-03 Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells Maggi, Jaxaira Schinnerling, Katina Pesce, Bárbara Hilkens, Catharien M. Catalán, Diego Aguillón, Juan C. Front Immunol Immunology Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to exert immunomodulatory effects on naive and memory CD4(+) T cells in an antigen-specific manner. For this purpose, MPLA-tDCs were loaded with purified protein derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4(+) T cells. Lymphocytes were re-challenged with autologous PPD-pulsed mature DCs (mDCs), evaluating proliferation and cytokine production by flow cytometry. On primed-naive CD4(+) T cells, the expression of regulatory T cell markers was evaluated and their suppressive ability was assessed in autologous co-cultures with CD4(+) effector T cells and PPD-pulsed mDCs. We detected that memory CD4(+) T cells primed by MPLA-tDCs presented reduced proliferation and proinflammatory cytokine expression in response to PPD and were refractory to subsequent stimulation. Naive CD4(+) T cells were instructed by MPLA-tDCs to be hyporesponsive to antigen-specific restimulation and to suppress the induction of T helper cell type 1 and 17 responses. In conclusion, MPLA-tDCs are able to modulate antigen-specific responses of both naive and memory CD4(+) T cells and might be a promising strategy to “turn off” self-reactive CD4(+) effector T cells in autoimmunity. Frontiers Media S.A. 2016-09-19 /pmc/articles/PMC5027201/ /pubmed/27698654 http://dx.doi.org/10.3389/fimmu.2016.00359 Text en Copyright © 2016 Maggi, Schinnerling, Pesce, Hilkens, Catalán and Aguillón. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Maggi, Jaxaira
Schinnerling, Katina
Pesce, Bárbara
Hilkens, Catharien M.
Catalán, Diego
Aguillón, Juan C.
Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells
title Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells
title_full Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells
title_fullStr Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells
title_full_unstemmed Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells
title_short Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4(+) T Cells
title_sort dexamethasone and monophosphoryl lipid a-modulated dendritic cells promote antigen-specific tolerogenic properties on naive and memory cd4(+) t cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027201/
https://www.ncbi.nlm.nih.gov/pubmed/27698654
http://dx.doi.org/10.3389/fimmu.2016.00359
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