CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity

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Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadmin …"><meta name="keywords" content="pmid:9362523, PMC2199137, doi:10.1084/jem.186.10.1623, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., R S Chu, O S Targoni, C V Harding, Adjuvants, Immunologic / genetics*, Animals, Antibody Specificity, Chickens, CpG Islands / immunology*, Cytokines / biosynthesis, Epitopes / immunology, Immunity, Cellular, Immunoglobulin G / biosynthesis, Immunoglobulin Isotypes / biosynthesis, Injections, Intraperitoneal, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Muramidase / immunology, Oligodeoxyribonucleotides / administration & dosage, Oligodeoxyribonucleotides / immunology, Species Specificity, Th1 Cells / immunology*, Th1 Cells / metabolism, Thionucleotides / administration & dosage, Thionucleotides / immunology, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/9362523/"><meta property="og:description" content="Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadmin …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/9362523/"><meta name="twitter:description" content="Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadmin …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">  <link rel="search" type="application/opensearchdescription+xml" href="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/opensearch.xml" title="PubMed search">  <noscript> <link rel="stylesheet" type="text/css" href="https://cdn.ncbi.nlm.nih.gov/pubmed/0d576970-ea4f-4f8d-9bab-bf51569c42d2/core/no-script.css"> </noscript> <meta name="citation_title" content="CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity"> <meta name="citation_authors" content="Chu RS;Targoni OS;Krieg AM;Lehmann PV;Harding CV;"> <meta name="citation_date" content="11/17/1997"> <meta name="citation_publisher" content="J Exp Med"> <meta name="citation_journal_title" content="The Journal of experimental medicine"> <meta name="citation_pmid" content="9362523"> <meta name="citation_abstract_html_url" content="https://pubmed.ncbi.nlm.nih.gov/9362523/"> <meta name="citation_volume" content="186"> <meta name="citation_issue" content="10"> <meta name="citation_doi" content="10.1084/jem.186.10.1623"> <meta name="citation_issn" content="0022-1007"> <link rel="canonical" href="https://pubmed.ncbi.nlm.nih.gov/9362523/" /> </head> <body > <noscript> <div class="no-script-banner" id="no-script-banner"> <div class="warning-message"> <div class="warning-message-text"> This site needs JavaScript to work properly. 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new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="5fJQdcjuZewB93bF6Tnf5Rl4d2XTcI3PiMjp8Gzqy3iPbVu4Y7nQMr7WeMCZbEry"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="5fJQdcjuZewB93bF6Tnf5Rl4d2XTcI3PiMjp8Gzqy3iPbVu4Y7nQMr7WeMCZbEry"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="5fJQdcjuZewB93bF6Tnf5Rl4d2XTcI3PiMjp8Gzqy3iPbVu4Y7nQMr7WeMCZbEry"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="5fJQdcjuZewB93bF6Tnf5Rl4d2XTcI3PiMjp8Gzqy3iPbVu4Y7nQMr7WeMCZbEry"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="9362523"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" 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data-collections-open-dialog-enabled="false" data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F9362523%2F%23open-collections-dialog" data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog" class="dialog collections-dialog" aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form" class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-existing-collections-url="/list-existing-collections/" data-add-to-existing-collection-url="/add-to-existing-collection/" data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/" data-myncbi-max-collection-name-length="100" data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="5fJQdcjuZewB93bF6Tnf5Rl4d2XTcI3PiMjp8Gzqy3iPbVu4Y7nQMr7WeMCZbEry"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" 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data-ga-label="R S Chu">R S Chu</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Targoni+OS&cauthor_id=9362523" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="O S Targoni">O S Targoni</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Krieg+AM&cauthor_id=9362523" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="A M Krieg">A M Krieg</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Lehmann+PV&cauthor_id=9362523" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="P V Lehmann">P V Lehmann</a><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Harding+CV&cauthor_id=9362523" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="C V Harding">C V Harding</a></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliation </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">9362523</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" 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id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-gamma. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-gamma secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non-CpG ODN did not induce IFN-gamma or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity. </p> </div> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/38c8b6a50b4d/JEM.970781f1.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="770" data-image-height="773" data-image-alt="Figure 1" data-pmc-id="PMC2199137" data-figure-id="F1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/b41f68572e1f/JEM.970781f1.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="770"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="773"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Th1-associated antigen-specific IgG2a responses are… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Th1-associated antigen-specific IgG2a responses are induced by immunization of BALB/c mice with IFA-HEL-CpG… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1 </strong> <div class="figure-caption-contents">Th1-associated antigen-specific IgG2a responses are induced by immunization of BALB/c mice with IFA-HEL-CpG ODN but not IFA-HEL-non–CpG ODN. (<i>A–C</i>). Mice were injected i.p. with CFA-HEL (a control for a Th1-dominated response), IFA-HEL (a control for a Th2-dominated response), or IFA-HEL with 100 μg of CpG ODN 1826 or non–CpG ODN 1745. Sera were collected from mice 15–18 d after injection and assayed by ELISA for: (<i>A</i>) anti-HEL IgG2a, an isotype associated with Th1-dominated responses; (<i>B</i>) anti-HEL IgG1; and (<i>C</i>) anti-HEL total Ig response. <i>A–C</i> represent data from a single experiment representative of three similar experiments. (<i>D</i>) BALB/c mice were immunized as above, except that 30 μg of CpG ODN 1585, non–CpG ODN 1972, CpG ODN 1760, or non–CpG ODN 1908 was used for each mouse. Anti-HEL IgG2a antibodies were detected by serum ELISA. Data shown in <i>D</i> are representative of three similar experiments.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/48fd9e37fb44/JEM.970781f2.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="748" data-image-height="1200" data-image-alt="Figure 2" data-pmc-id="PMC2199137" data-figure-id="F2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/cfb326aa3d52/JEM.970781f2.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="748"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1200"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> CpG ODN enhance HEL-specific IFN-γ… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> CpG ODN enhance HEL-specific IFN-γ production by BALB/c splenocytes. Mice were immunized as… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2 </strong> <div class="figure-caption-contents">CpG ODN enhance HEL-specific IFN-γ production by BALB/c splenocytes. Mice were immunized as in Fig. 1 with 100 μg ODN/mouse in <i>A</i> and 30 μg ODN/mouse in panel B. After 3 wk, splenocytes were isolated and incubated with HEL (<i>closed circles</i>) or medium alone (<i>open circles</i>). ELISA spot assay was performed and spots were quantitated by a computerized image analysis program. Each point represents the mean number of spots per well for one mouse (assayed in duplicate); horizontal bars indicate the mean of points for each group of mice. Similar results were observed in five independent experiments with CpG- and non–CpG ODN in BALB/c mice.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/5fa4da7dc974/JEM.970781f3.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="629" data-image-height="220" data-image-alt="Figure 3" data-pmc-id="PMC2199137" data-figure-id="F3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/af88a617f96a/JEM.970781f3.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="629"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="220"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> ELISA spot assessment of IFN-γ… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> ELISA spot assessment of IFN-γ production by splenocytes from immunized BALB/c mice. Pictures… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3 </strong> <div class="figure-caption-contents">ELISA spot assessment of IFN-γ production by splenocytes from immunized BALB/c mice. Pictures show representative images of ELISA spot wells from the experiment shown in Fig. 2 <i>A</i>. The number of spots, as quantitated by an image analysis program, is indicated next to each well. Each well contained HEL (100 μg/ml) and 10<sup>6</sup> splenocytes isolated from mice immunized with IFA-HEL (<i>A</i>), IFA-HEL-non–CpG ODN 1745 (<i>B</i>) or IFA-HEL-CpG ODN 1826 (<i>C</i>).</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/f8d5b669c4e7/JEM.970781f4.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="755" data-image-height="1199" data-image-alt="Figure 4" data-pmc-id="PMC2199137" data-figure-id="F4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/07a03a7a0569/JEM.970781f4.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="755"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1199"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> CpG ODN decrease HEL-specific IL-5… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> CpG ODN decrease HEL-specific IL-5 production by BALB/c splenocytes. Mice were immunized as… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4 </strong> <div class="figure-caption-contents">CpG ODN decrease HEL-specific IL-5 production by BALB/c splenocytes. Mice were immunized as in Fig. 2 (30 μg ODN/mouse), and splenocytes were harvested for in vitro restimulation with or without HEL. ELISA spot analysis was performed for IL-5. The data are representative of five similar experiments with CpG- and non–CpG ODN in BALB/c mice.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/1a820d4eb2a1/JEM.970781f5.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="720" data-image-height="538" data-image-alt="Figure 5" data-pmc-id="PMC2199137" data-figure-id="F5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c90/2199137/c889408a2ffb/JEM.970781f5.gif" alt="Figure 5" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="720"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="538"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5 </p> </strong> <div class="figure-caption-contents"><p> Induction of HEL-specific IFN-γ responses… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5 </p> </strong> <div class="figure-caption-contents"><p> Induction of HEL-specific IFN-γ responses by CpG ODN in B10.D2 mice. B10.D2 mice… </p></div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5 </strong> <div class="figure-caption-contents">Induction of HEL-specific IFN-γ responses by CpG ODN in B10.D2 mice. B10.D2 mice were immunized as in Fig. 1, except that ODN were used at 30 μg per mouse. Three weeks after immunization, HEL-specific production of IFN-γ by splenocytes was measured by ELISA spot assay as in Fig. 2. The data shown are representative of three similar experiments.</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/9551923/" ref="article_id=9551923&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="9551923" data-ga-label=""> CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Davis HL, Weeratna R, Waldschmidt TJ, Tygrett L, Schorr J, Krieg AM.</span> <span class="docsum-authors short-authors">Davis HL, et al.</span> <span class="docsum-journal-citation full-journal-citation">J Immunol. 1998 Jan 15;160(2):870-6.</span> <span class="docsum-journal-citation short-journal-citation">J Immunol. 1998.</span> <span class="citation-part">PMID: <span class="docsum-pmid">9551923</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/12443671/" ref="article_id=12443671&linksrc=similar_articles_link&ordinalpos=2" data-ga-category="similar_article" data-ga-action="12443671" data-ga-label=""> CpG-containing oligodeoxynucleotides, in combination with conventional adjuvants, enhance the magnitude and change the bias of the immune responses to a herpesvirus glycoprotein. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Ioannou XP, Gomis SM, Karvonen B, Hecker R, Babiuk LA, van Drunen Littel-van den Hurk S.</span> <span class="docsum-authors short-authors">Ioannou XP, et al.</span> <span class="docsum-journal-citation full-journal-citation">Vaccine. 2002 Nov 22;21(1-2):127-37. doi: 10.1016/s0264-410x(02)00378-x.</span> <span class="docsum-journal-citation short-journal-citation">Vaccine. 2002.</span> <span class="citation-part">PMID: <span class="docsum-pmid">12443671</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/17433075/" ref="article_id=17433075&linksrc=similar_articles_link&ordinalpos=3" data-ga-category="similar_article" data-ga-action="17433075" data-ga-label=""> Increased levels of interferon-gamma primed by culture filtrate proteins antigen and CpG-ODN immunization do not confer significant protection against Mycobacterium tuberculosis infection. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Fonseca DM, Silva CL, Paula MO, Soares EG, Marchal G, Horn C, Bonato VL.</span> <span class="docsum-authors short-authors">Fonseca DM, et al.</span> <span class="docsum-journal-citation full-journal-citation">Immunology. 2007 Aug;121(4):508-17. doi: 10.1111/j.1365-2567.2007.02597.x. 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Immunol Today. 1995;16:374–379. - <a class="reference-link" href="/7546192/" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="7546192" > PubMed </a> </li> </ol> </li> </ol> <div class="actions-bar"> <button class="show-all" ref="linksrc=show_all_references_link" aria-controls="top-references-list-1" data-next-page-url="/9362523/references/" data-ga-category="reference" data-ga-action="show_more" > Show all 37 references </button> </div> </div> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 class="title"> Publication types </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Research Support, U.S. Gov't, Non-P.H.S." tabindex="0" aria-controls="keyword-actions-publication-types-0" aria-expanded="false" data-pinger-ignore> Research Support, U.S. Gov't, Non-P.H.S. </button><div 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Antibody Specificity"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Antibody+Specificity%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Antibody+Specificity%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Antibody Specificity"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Antibody Specificity"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Antibody+Specificity" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Antibody Specificity"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Antibody Specificity"[MeSH]" data-ga-category="search" 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href="/?term=%22Adjuvants%2C+Immunologic%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Adjuvants%2C+Immunologic%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Adjuvants, Immunologic"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Adjuvants, Immunologic"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Adjuvants%2C+Immunologic%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Adjuvants, Immunologic"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Adjuvants, Immunologic"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Adjuvants, Immunologic"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Cytokines" tabindex="0" aria-controls="keyword-actions-substances-1" aria-expanded="false" data-pinger-ignore> Cytokines </button><div id="keyword-actions-substances-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Cytokines"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Cytokines%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Cytokines%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Cytokines"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Cytokines"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" 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class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Epitopes%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Epitopes%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Epitopes"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Epitopes"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Epitopes%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Epitopes"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Epitopes"[nm]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Epitopes"[nm]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger 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CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity - PubMed