Activation outcomes induced in naïve CD8 T-cells by macrophages primed via "phagocytic" and nonphagocytic pathways

The array of phagocytic receptors expressed by macrophages make them very efficient at pathogen clearance, and the phagocytic process links innate with adaptive immunity. Primary macrophages modulate antigen cross-presentation and T-cell activation. We assessed ex vivo the putative role of different...

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Veröffentlicht in:Molecular biology of the cell 2008-02, Vol.19 (2), p.701-710
Hauptverfasser: Olazabal, Isabel María, Martín-Cofreces, Noa Beatriz, Mittelbrunn, María, Martínez del Hoyo, Gloria, Alarcón, Balbino, Sánchez-Madrid, Francisco
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container_end_page 710
container_issue 2
container_start_page 701
container_title Molecular biology of the cell
container_volume 19
creator Olazabal, Isabel María
Martín-Cofreces, Noa Beatriz
Mittelbrunn, María
Martínez del Hoyo, Gloria
Alarcón, Balbino
Sánchez-Madrid, Francisco
description The array of phagocytic receptors expressed by macrophages make them very efficient at pathogen clearance, and the phagocytic process links innate with adaptive immunity. Primary macrophages modulate antigen cross-presentation and T-cell activation. We assessed ex vivo the putative role of different phagocytic receptors in immune synapse formation with CD8 naïve T-cells from OT-I transgenic mice and compared this with the administration of antigen as a soluble peptide. Macrophages that have phagocytosed antigen induce T-cell microtubule-organizing center and F-actin cytoskeleton relocalization to the contact site, as well as the recruitment of proximal T-cell receptor signals such as activated Vav1 and PKC. At the same doses of loaded antigen (1 microM), "phagocytic" macrophages were more efficient than peptide-antigen-loaded macrophages at forming productive immune synapses with T-cells, as indicated by active T-cell TCR/CD3 conformation, LAT phosphorylation, IL-2 production, and T-cell proliferation. Similar T-cell proliferation efficiency was obtained when low doses of soluble peptide (3-30 nM) were loaded on macrophages. These results suggest that the pathway used for antigen uptake may modulate the antigen density presented on MHC-I, resulting in different signals induced in naïve CD8 T-cells, leading either to CD8 T-cell activation or anergy.
doi_str_mv 10.1091/mbc.E07-07-0650
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subjects Animals
Antigens, CD - metabolism
Antigens, Differentiation, T-Lymphocyte - metabolism
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cell Proliferation
Cross-Priming - immunology
Interferon-gamma - biosynthesis
Interleukin-2 - biosynthesis
Interleukin-2 Receptor alpha Subunit - metabolism
Lectins, C-Type
Macrophages - cytology
Macrophages - immunology
Mice
Ovalbumin
Peptides - immunology
Phagocytosis
title Activation outcomes induced in naïve CD8 T-cells by macrophages primed via "phagocytic" and nonphagocytic pathways
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