Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells
Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of c...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-05, Vol.109 (20), p.7835-7840 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Sanderson, Nicholas Stephen Rennie Puntel, Mariana Kroeger, Kurt M. Bondale, Niyati S. Swerdlow, Mark Iranmanesh, Niloufar Yagita, Hideo Ibrahim, Ahmed Castro, Maria G. Lowenstein, Pedro R. |
| description | Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread. |
| doi_str_mv | 10.1073/pnas.1116058109 |
| format | Article |
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It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1116058109</identifier><identifier>PMID: 22547816</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adenoviridae ; Analysis of Variance ; antigens ; Astrocytes ; Astrocytes - immunology ; B lymphocytes ; Biological Sciences ; CD8 antigen ; Cell nucleus ; Cellular immunity ; Coculture techniques ; Computed tomography ; Cytokines ; Cytotoxicity ; Effector cells ; gamma -Interferon ; Genetic Vectors ; Genetic Vectors - genetics ; genetics ; Green Fluorescent Proteins ; image analysis ; Image Processing, Computer-Assisted ; Immunological Synapses ; Immunological Synapses - immunology ; immunology ; interferon-gamma ; Interferon-gamma - immunology ; Interferon-gamma - metabolism ; Lymphocytes T ; metabolism ; methods ; Microscopy ; Microscopy - methods ; prediction ; Secretion ; synapse ; Synapses ; T lymphocytes ; T-Lymphocytes, Cytotoxic ; T-Lymphocytes, Cytotoxic - immunology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-05, Vol.109 (20), p.7835-7840</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-df39dce3fc606cd453cd5e84b8615d4bb1edc70a90f5df520046910ae02daf2c3</citedby><cites>FETCH-LOGICAL-c505t-df39dce3fc606cd453cd5e84b8615d4bb1edc70a90f5df520046910ae02daf2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/20.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41592757$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41592757$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22547816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sanderson, Nicholas Stephen Rennie</creatorcontrib><creatorcontrib>Puntel, Mariana</creatorcontrib><creatorcontrib>Kroeger, Kurt M.</creatorcontrib><creatorcontrib>Bondale, Niyati S.</creatorcontrib><creatorcontrib>Swerdlow, Mark</creatorcontrib><creatorcontrib>Iranmanesh, Niloufar</creatorcontrib><creatorcontrib>Yagita, Hideo</creatorcontrib><creatorcontrib>Ibrahim, Ahmed</creatorcontrib><creatorcontrib>Castro, Maria G.</creatorcontrib><creatorcontrib>Lowenstein, Pedro R.</creatorcontrib><title>Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.</description><subject>Adenoviridae</subject><subject>Analysis of Variance</subject><subject>antigens</subject><subject>Astrocytes</subject><subject>Astrocytes - immunology</subject><subject>B lymphocytes</subject><subject>Biological Sciences</subject><subject>CD8 antigen</subject><subject>Cell nucleus</subject><subject>Cellular immunity</subject><subject>Coculture techniques</subject><subject>Computed tomography</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Effector cells</subject><subject>gamma -Interferon</subject><subject>Genetic Vectors</subject><subject>Genetic Vectors - genetics</subject><subject>genetics</subject><subject>Green Fluorescent Proteins</subject><subject>image analysis</subject><subject>Image Processing, Computer-Assisted</subject><subject>Immunological Synapses</subject><subject>Immunological Synapses - immunology</subject><subject>immunology</subject><subject>interferon-gamma</subject><subject>Interferon-gamma - immunology</subject><subject>Interferon-gamma - metabolism</subject><subject>Lymphocytes T</subject><subject>metabolism</subject><subject>methods</subject><subject>Microscopy</subject><subject>Microscopy - methods</subject><subject>prediction</subject><subject>Secretion</subject><subject>synapse</subject><subject>Synapses</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes, Cytotoxic</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkb9uFDEQxi1ERI5ATQW4TLPJ-O_uNkjoRAApUppQWz6vfXG0ax-2L-Kei_fgmfDqjgtUYQpP4d98M58-hN4QuCDQsstN0PmCECJBdAT6Z2hRX9JI3sNztACgbdNxyk_Ry5zvAaAXHbxAp5QK3nZELpBb7kos8Yc32E_TNsQxrr3RI867oDfZZjxEHGLByeaSvCm43FmsTfEx4OiwD8UmZ1MMza-fuESsQ_FrG6pe0WltCzZ2HPMrdOL0mO3rQz9D364-3S6_NNc3n78uP143RoAozeBYPxjLnJEgzcAFM4OwHV91koiBr1bEDqYF3YMTgxMUgMuegLZAB-2oYWfow153s11NlbWhJD2qTfKTTjsVtVf__gR_p9bxQTEmpGS8CpwfBFL8vq2e1eTzbEEHG7dZkb6W6ISgT6NAoeOMCvkfKOGEACeiopd71KSYc7LueDwBNWeu5szVY-Z14t3fno_8n5Ar8P4AzJOPcr2ioNqOzUvf7on7XGI6IvWenraiZb8BWju_JQ</recordid><startdate>20120515</startdate><enddate>20120515</enddate><creator>Sanderson, Nicholas Stephen Rennie</creator><creator>Puntel, Mariana</creator><creator>Kroeger, Kurt M.</creator><creator>Bondale, Niyati S.</creator><creator>Swerdlow, Mark</creator><creator>Iranmanesh, Niloufar</creator><creator>Yagita, Hideo</creator><creator>Ibrahim, Ahmed</creator><creator>Castro, Maria G.</creator><creator>Lowenstein, Pedro R.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7T5</scope><scope>H94</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20120515</creationdate><title>Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells</title><author>Sanderson, Nicholas Stephen Rennie ; Puntel, Mariana ; Kroeger, Kurt M. ; Bondale, Niyati S. ; Swerdlow, Mark ; Iranmanesh, Niloufar ; Yagita, Hideo ; Ibrahim, Ahmed ; Castro, Maria G. ; Lowenstein, Pedro R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-df39dce3fc606cd453cd5e84b8615d4bb1edc70a90f5df520046910ae02daf2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenoviridae</topic><topic>Analysis of Variance</topic><topic>antigens</topic><topic>Astrocytes</topic><topic>Astrocytes - immunology</topic><topic>B lymphocytes</topic><topic>Biological Sciences</topic><topic>CD8 antigen</topic><topic>Cell nucleus</topic><topic>Cellular immunity</topic><topic>Coculture techniques</topic><topic>Computed tomography</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Effector cells</topic><topic>gamma -Interferon</topic><topic>Genetic Vectors</topic><topic>Genetic Vectors - genetics</topic><topic>genetics</topic><topic>Green Fluorescent Proteins</topic><topic>image analysis</topic><topic>Image Processing, Computer-Assisted</topic><topic>Immunological Synapses</topic><topic>Immunological Synapses - immunology</topic><topic>immunology</topic><topic>interferon-gamma</topic><topic>Interferon-gamma - immunology</topic><topic>Interferon-gamma - metabolism</topic><topic>Lymphocytes T</topic><topic>metabolism</topic><topic>methods</topic><topic>Microscopy</topic><topic>Microscopy - methods</topic><topic>prediction</topic><topic>Secretion</topic><topic>synapse</topic><topic>Synapses</topic><topic>T lymphocytes</topic><topic>T-Lymphocytes, Cytotoxic</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sanderson, Nicholas Stephen Rennie</creatorcontrib><creatorcontrib>Puntel, Mariana</creatorcontrib><creatorcontrib>Kroeger, Kurt M.</creatorcontrib><creatorcontrib>Bondale, Niyati S.</creatorcontrib><creatorcontrib>Swerdlow, Mark</creatorcontrib><creatorcontrib>Iranmanesh, Niloufar</creatorcontrib><creatorcontrib>Yagita, Hideo</creatorcontrib><creatorcontrib>Ibrahim, Ahmed</creatorcontrib><creatorcontrib>Castro, Maria G.</creatorcontrib><creatorcontrib>Lowenstein, Pedro R.</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanderson, Nicholas Stephen Rennie</au><au>Puntel, Mariana</au><au>Kroeger, Kurt M.</au><au>Bondale, Niyati S.</au><au>Swerdlow, Mark</au><au>Iranmanesh, Niloufar</au><au>Yagita, Hideo</au><au>Ibrahim, Ahmed</au><au>Castro, Maria G.</au><au>Lowenstein, Pedro R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2012-05-15</date><risdate>2012</risdate><volume>109</volume><issue>20</issue><spage>7835</spage><epage>7840</epage><pages>7835-7840</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22547816</pmid><doi>10.1073/pnas.1116058109</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2012-05, Vol.109 (20), p.7835-7840 |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adenoviridae Analysis of Variance antigens Astrocytes Astrocytes - immunology B lymphocytes Biological Sciences CD8 antigen Cell nucleus Cellular immunity Coculture techniques Computed tomography Cytokines Cytotoxicity Effector cells gamma -Interferon Genetic Vectors Genetic Vectors - genetics genetics Green Fluorescent Proteins image analysis Image Processing, Computer-Assisted Immunological Synapses Immunological Synapses - immunology immunology interferon-gamma Interferon-gamma - immunology Interferon-gamma - metabolism Lymphocytes T metabolism methods Microscopy Microscopy - methods prediction Secretion synapse Synapses T lymphocytes T-Lymphocytes, Cytotoxic T-Lymphocytes, Cytotoxic - immunology |
| title | Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells |
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