{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:54:53Z","timestamp":1759730093561},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,2,18]],"date-time":"2004-02-18T00:00:00Z","timestamp":1077062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Protection against infections with<jats:italic> Streptococcus pneumoniae<\/jats:italic> is mediated by antibodies against the capsular polysaccharides (caps\u2010PS). Here we show that in <jats:italic>in vitro<\/jats:italic> experiments CD4<jats:sup>+<\/jats:sup> T\u2004lymphocytes stimulate and CD8<jats:sup>+<\/jats:sup> T\u2004lymphocytes inhibit the human anti\u2010caps\u2010PS antibody response. Using antagonistic anti\u2010CD40 and antagonistic anti\u2010CD40\u2004ligand (CD40L) monoclonal antibodies, we showed that the CD4<jats:sup>+<\/jats:sup> T\u2004lymphocyte\u2010mediated stimulation is dependent on the CD40\u2010CD40L interaction. The role of CD40L was further illustrated by the observation that CD4<jats:sup>+<\/jats:sup> T\u2004lymphocytes obtained from a patient with hyper\u2010IgM syndrome were unable to enhance the immune response to caps\u2010PS. Furthermore, CD4<jats:sup>+<\/jats:sup> T\u2004lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps\u2010PS, failed to stimulate the antibody response of adult B\u2004lymphocytes to caps\u2010PS.\nThese <jats:italic>in vitro<\/jats:italic> findings were confirmed by <jats:italic>in vivo<\/jats:italic> experiments in which <jats:italic>SCID\/SCID<\/jats:italic> mice were reconstituted with human mononuclear cells. Furthermore, we showed that caps\u2010PS induce production of IL\u20104, IL\u20106, IL\u201010, and IFN\u2010\u03b3, and that thisenhanced production was inhibited by blocking the CD40\u2010CD40L interaction. This is the first demonstration that the human immune response to caps\u2010PS, which is markedly regulated by T\u2004lymphocytes, is dependent on the CD40\u2010CD40L interaction.<\/jats:p>","DOI":"10.1002\/eji.200324381","type":"journal-article","created":{"date-parts":[[2004,2,26]],"date-time":"2004-02-26T20:25:09Z","timestamp":1077827109000},"page":"850-858","source":"Crossref","is-referenced-by-count":23,"title":["The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40\u2010CD40 ligand interaction"],"prefix":"10.1002","volume":"34","author":[{"given":"Axel","family":"Jeurissen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greet","family":"Wuyts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Kasran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seema","family":"Ramdien\u2010Murli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Blanckaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Boon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan\u2004L.","family":"Ceuppens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Bossuyt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2,25]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408419109113510"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/14.1.251"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4049\/jimmunol.135.1.1","article-title":"Pneumococcal polysaccharides induce antibody formation by human B\u2004lymphocytes in vitro.","volume":"135","author":"Rijkers G. 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