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Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection
Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of imm...
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| Published in: | Immunity (Cambridge, Mass.) Mass.), 2015-02, Vol.42 (2), p.379-390 |
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| Main Authors: | , , , , , , , |
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| cites | cdi_FETCH-LOGICAL-c441t-25f72d1a3c37c4a28ed2901362d0ac2bcf024d1b0eac834e24769497b20131bb3 |
| container_end_page | 390 |
| container_issue | 2 |
| container_start_page | 379 |
| container_title | Immunity (Cambridge, Mass.) |
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| creator | Yamada, Douglas H Elsaesser, Heidi Lux, Anja Timmerman, John M Morrison, Sherie L de la Torre, Juan Carlos Nimmerjahn, Falk Brooks, David G |
| description | Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control. |
| doi_str_mv | 10.1016/j.immuni.2015.01.005 |
| format | article |
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T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2015.01.005</identifier><identifier>PMID: 25680277</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antibodies, Monoclonal, Murine-Derived - pharmacology ; Antibodies, Viral - immunology ; Antigen-Antibody Complex - immunology ; Antigens, CD20 - biosynthesis ; Antigens, CD20 - immunology ; B-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - immunology ; Cross-Priming - immunology ; Dendritic Cells - immunology ; Immune Evasion - immunology ; Immune Tolerance - immunology ; Immunologic Factors - pharmacology ; Lymphocyte Activation - immunology ; Lymphocyte Depletion ; Lymphocytic Choriomeningitis - immunology ; Lymphocytic Choriomeningitis - virology ; Lymphocytic choriomeningitis virus ; Lymphocytic choriomeningitis virus - immunology ; Macrophages - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phagocytosis - immunology ; Receptors, IgG - antagonists & inhibitors ; Receptors, IgG - immunology ; Rituximab</subject><ispartof>Immunity (Cambridge, Mass.), 2015-02, Vol.42 (2), p.379-390</ispartof><rights>Copyright © 2015 Elsevier Inc. 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All rights reserved. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-25f72d1a3c37c4a28ed2901362d0ac2bcf024d1b0eac834e24769497b20131bb3</citedby><cites>FETCH-LOGICAL-c441t-25f72d1a3c37c4a28ed2901362d0ac2bcf024d1b0eac834e24769497b20131bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25680277$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Douglas H</creatorcontrib><creatorcontrib>Elsaesser, Heidi</creatorcontrib><creatorcontrib>Lux, Anja</creatorcontrib><creatorcontrib>Timmerman, John M</creatorcontrib><creatorcontrib>Morrison, Sherie L</creatorcontrib><creatorcontrib>de la Torre, Juan Carlos</creatorcontrib><creatorcontrib>Nimmerjahn, Falk</creatorcontrib><creatorcontrib>Brooks, David G</creatorcontrib><title>Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.</description><subject>Animals</subject><subject>Antibodies, Monoclonal, Murine-Derived - pharmacology</subject><subject>Antibodies, Viral - immunology</subject><subject>Antigen-Antibody Complex - immunology</subject><subject>Antigens, CD20 - biosynthesis</subject><subject>Antigens, CD20 - immunology</subject><subject>B-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cross-Priming - immunology</subject><subject>Dendritic Cells - immunology</subject><subject>Immune Evasion - immunology</subject><subject>Immune Tolerance - immunology</subject><subject>Immunologic Factors - pharmacology</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocyte Depletion</subject><subject>Lymphocytic Choriomeningitis - immunology</subject><subject>Lymphocytic Choriomeningitis - virology</subject><subject>Lymphocytic choriomeningitis virus</subject><subject>Lymphocytic choriomeningitis virus - immunology</subject><subject>Macrophages - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Phagocytosis - immunology</subject><subject>Receptors, IgG - antagonists & inhibitors</subject><subject>Receptors, IgG - immunology</subject><subject>Rituximab</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqNkcFq3TAQRUVoSdK0f1CKl93YnZFk63kTCKFJC4EsmqyFLI9TPZ4lR7ID-a7-R78pMi8N6S6rGZh7L3c4jH1GqBCw-bat3Dgu3lUcsK4AK4D6gB0jtKqUuIF3665kqRoUR-xDSlsAlHULh-yI180GuFLHrPu1TFOklFzwRRiKC_v3TxnJ0jSHWI7UOzNTXxg_uy70jwUNA9l8KobF23k19Ut0_q6YKCaXZvJz8eCi2RXOr8qs-MjeD2aX6NPzPGG3F99vzn-UV9eXP8_PrkorJc4lrwfFezTCCmWl4RvqeQsoGt6DsbyzA3DZYwdk7EZI4lI1rWxVl_8X2HXihJ3uc6ely8VtrpJ76Cm60cRHHYzT_1-8-63vwoOWQkglVA74-hwQw_1CadajS5Z2O-MpLElj00iOHBp4g7RWgkvJeZbKvdTGkFKk4aURgl5J6q3ek9QrSQ2oM8ls-_L6mxfTP3TiCYg3n1Y</recordid><startdate>20150217</startdate><enddate>20150217</enddate><creator>Yamada, Douglas H</creator><creator>Elsaesser, Heidi</creator><creator>Lux, Anja</creator><creator>Timmerman, John M</creator><creator>Morrison, Sherie L</creator><creator>de la Torre, Juan Carlos</creator><creator>Nimmerjahn, Falk</creator><creator>Brooks, David G</creator><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>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20150217</creationdate><title>Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection</title><author>Yamada, Douglas H ; 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| ispartof | Immunity (Cambridge, Mass.), 2015-02, Vol.42 (2), p.379-390 |
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| language | eng |
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| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | Animals Antibodies, Monoclonal, Murine-Derived - pharmacology Antibodies, Viral - immunology Antigen-Antibody Complex - immunology Antigens, CD20 - biosynthesis Antigens, CD20 - immunology B-Lymphocytes - immunology CD4-Positive T-Lymphocytes - immunology Cross-Priming - immunology Dendritic Cells - immunology Immune Evasion - immunology Immune Tolerance - immunology Immunologic Factors - pharmacology Lymphocyte Activation - immunology Lymphocyte Depletion Lymphocytic Choriomeningitis - immunology Lymphocytic Choriomeningitis - virology Lymphocytic choriomeningitis virus Lymphocytic choriomeningitis virus - immunology Macrophages - immunology Mice Mice, Inbred C57BL Mice, Knockout Phagocytosis - immunology Receptors, IgG - antagonists & inhibitors Receptors, IgG - immunology Rituximab |
| title | Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection |
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