title: Activation outcomes induced in naïve CD8 T-cells by macrophages primed via "phagocytic" and nonphagocytic pathways.
abstract: 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.
authors: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain.
authors: Isabel María
authors: IM
authors: Olazabal
authors: Noa Beatriz
authors: NB
authors: Martín-Cofreces
authors: María
authors: M
authors: Mittelbrunn
authors: Gloria
authors: G
authors: Martínez del Hoyo
authors: Balbino
authors: B
authors: Alarcón
authors: Francisco
authors: F
authors: Sánchez-Madrid
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D049109:Cell Proliferation; D045142:Cross-Priming / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D010047:Ovalbumin; D010455:Peptides / Q000276:immunology; D010587:Phagocytosis; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D010047:Ovalbumin; D010455:Peptides; D000099192:CD69 Antigens