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 |
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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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Silvio</contributor><creatorcontrib>Olazabal, Isabel María ; Martín-Cofreces, Noa Beatriz ; Mittelbrunn, María ; Martínez del Hoyo, Gloria ; Alarcón, Balbino ; Sánchez-Madrid, Francisco ; Gutkind, J. Silvio</creatorcontrib><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.</description><identifier>ISSN: 1059-1524</identifier><identifier>EISSN: 1939-4586</identifier><identifier>DOI: 10.1091/mbc.E07-07-0650</identifier><identifier>PMID: 18077558</identifier><language>eng</language><publisher>United States: The American Society for Cell Biology</publisher><subject>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</subject><ispartof>Molecular biology of the cell, 2008-02, Vol.19 (2), p.701-710</ispartof><rights>2008 by The American Society for Cell Biology 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-1fca0c640eaf74633efef612a8392b26bec7ab96f36a78ff7611f0b9c99df9c43</citedby><cites>FETCH-LOGICAL-c467t-1fca0c640eaf74633efef612a8392b26bec7ab96f36a78ff7611f0b9c99df9c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230587/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230587/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18077558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gutkind, J. Silvio</contributor><creatorcontrib>Olazabal, Isabel María</creatorcontrib><creatorcontrib>Martín-Cofreces, Noa Beatriz</creatorcontrib><creatorcontrib>Mittelbrunn, María</creatorcontrib><creatorcontrib>Martínez del Hoyo, Gloria</creatorcontrib><creatorcontrib>Alarcón, Balbino</creatorcontrib><creatorcontrib>Sánchez-Madrid, Francisco</creatorcontrib><title>Activation outcomes induced in naïve CD8 T-cells by macrophages primed via "phagocytic" and nonphagocytic pathways</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><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.</description><subject>Animals</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, T-Lymphocyte - metabolism</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Proliferation</subject><subject>Cross-Priming - immunology</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-2 - biosynthesis</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Lectins, C-Type</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Mice</subject><subject>Ovalbumin</subject><subject>Peptides - immunology</subject><subject>Phagocytosis</subject><issn>1059-1524</issn><issn>1939-4586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctKxDAUhoMozji6difBhbs6SS9JsxFkvILgRtfhNJM4kTapTTsyT-VD-GKmOHiBAyecfPnzc36Ejik5p0TQeVOp82vCk7FYQXbQlIpMJHlRst14JoVIaJHmE3QQwishNM8Z30cTWhLOi6KconCperuG3nqH_dAr3-iArVsOSi9jxw4-P9YaL65K_JQoXdcBVxvcgOp8u4KXCLedbSK7toBPx5FXm96qUwxuiZ13vyPcQr96h004RHsG6qCPtn2Gnm-unxZ3ycPj7f3i8iFR0WWfUKOAKJYTDYbnLMu00YbRFMpMpFXKKq04VIKZjAEvjeGMUkMqoYRYGqHybIYuvnXboYoWlXZ9B7UcDUO3kR6s_H_j7Eq--LVM04wUJY8CZ1uBzr8NOvSysWFcAjjthyA5SZkgOY3g_BuMawmh0-bnE0rkGJSMQUlNuBwrBhVfnPz19stvk8m-AASck2E</recordid><startdate>200802</startdate><enddate>200802</enddate><creator>Olazabal, Isabel María</creator><creator>Martín-Cofreces, Noa Beatriz</creator><creator>Mittelbrunn, María</creator><creator>Martínez del Hoyo, Gloria</creator><creator>Alarcón, Balbino</creator><creator>Sánchez-Madrid, Francisco</creator><general>The American Society for Cell Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200802</creationdate><title>Activation outcomes induced in naïve CD8 T-cells by macrophages primed via "phagocytic" and nonphagocytic pathways</title><author>Olazabal, Isabel María ; Martín-Cofreces, Noa Beatriz ; Mittelbrunn, María ; Martínez del Hoyo, Gloria ; Alarcón, Balbino ; Sánchez-Madrid, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-1fca0c640eaf74633efef612a8392b26bec7ab96f36a78ff7611f0b9c99df9c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, Differentiation, T-Lymphocyte - metabolism</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Proliferation</topic><topic>Cross-Priming - immunology</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-2 - biosynthesis</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Lectins, C-Type</topic><topic>Macrophages - cytology</topic><topic>Macrophages - immunology</topic><topic>Mice</topic><topic>Ovalbumin</topic><topic>Peptides - immunology</topic><topic>Phagocytosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olazabal, Isabel María</creatorcontrib><creatorcontrib>Martín-Cofreces, Noa Beatriz</creatorcontrib><creatorcontrib>Mittelbrunn, María</creatorcontrib><creatorcontrib>Martínez del Hoyo, Gloria</creatorcontrib><creatorcontrib>Alarcón, Balbino</creatorcontrib><creatorcontrib>Sánchez-Madrid, Francisco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olazabal, Isabel María</au><au>Martín-Cofreces, Noa Beatriz</au><au>Mittelbrunn, María</au><au>Martínez del Hoyo, Gloria</au><au>Alarcón, Balbino</au><au>Sánchez-Madrid, Francisco</au><au>Gutkind, J. Silvio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation outcomes induced in naïve CD8 T-cells by macrophages primed via "phagocytic" and nonphagocytic pathways</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2008-02</date><risdate>2008</risdate><volume>19</volume><issue>2</issue><spage>701</spage><epage>710</epage><pages>701-710</pages><issn>1059-1524</issn><eissn>1939-4586</eissn><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.</abstract><cop>United States</cop><pub>The American Society for Cell Biology</pub><pmid>18077558</pmid><doi>10.1091/mbc.E07-07-0650</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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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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