title: Dexamethasone and Monophosphoryl Lipid A-Modulated Dendritic Cells Promote Antigen-Specific Tolerogenic Properties on Naive and Memory CD4+T Cells.
abstract: 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.
authors.affiliation: Programa Disciplinario de Inmunología, Immune Regulation and Tolerance Research Group, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy (MIII), Santiago, Chile.
authors.forename: Jaxaira
authors.initials: J
authors.lastname: Maggi
authors.affiliation: Programa Disciplinario de Inmunología, Immune Regulation and Tolerance Research Group, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy (MIII), Santiago, Chile.
authors.forename: Katina
authors.initials: K
authors.lastname: Schinnerling
authors.affiliation: Programa Disciplinario de Inmunología, Immune Regulation and Tolerance Research Group, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile , Santiago , Chile.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Pesce
authors.affiliation: Musculoskeletal Research Group, Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Catharien M
authors.initials: CM
authors.lastname: Hilkens
authors.affiliation: Programa Disciplinario de Inmunología, Immune Regulation and Tolerance Research Group, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy (MIII), Santiago, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Catalán
authors.affiliation: Programa Disciplinario de Inmunología, Immune Regulation and Tolerance Research Group, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy (MIII), Santiago, Chile.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Aguillón
keywords: hyporesponsiveness; immunotherapy; memory CD4+ T cells; monocyte-derived dendritic cells; naive CD4+ T cells; tolerance