{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:09:28Z","timestamp":1760170168215},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T00:00:00Z","timestamp":1095811200000},"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":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CD8<jats:sup>+<\/jats:sup> T\u2004cells are killer cells but also major producers of IFN\u2010\u03b3. We have investigated the effects of peptide antigen titration and costimulatory blockade on IFN\u2010\u03b3 production and proliferation by naive CD8<jats:sup>+<\/jats:sup> T\u2004cells. Mature dendritic cells (DC) pulsed with high amounts of agonist peptide triggered proliferation but little IFN\u2010\u03b3 secretion in individual T\u2004cells. In contrast, immature DC pulsed with similar amounts of peptide induced IFN\u2010\u03b3 secretion in a larger fraction of T\u2004cells but triggered less proliferation. Blocking B7.2 or lowering the amount of peptide on mature DC led to a response similar to that induced by immature DC, suggesting that differences in stimulatory strength were responsible for the different responses. Using splenic antigen\u2010presenting cells (APC) we demonstrate that reducing the amount of peptide in combination with B7 blockage enhanced IFN\u2010\u03b3 secretion and decreased proliferation in naive CD8<jats:sup>+<\/jats:sup> T\u2004cells in an additive way. Our data suggest that IFN\u2010\u03b3 secretion and proliferation are independently and inversely controlled by stimulatory strength in naive CD8<jats:sup>+<\/jats:sup> T\u2004cells. This may enable CD8<jats:sup>+<\/jats:sup> T\u2004cells to respond with IFN\u2010\u03b3 secretion to immature APC with few peptide ligands consistent with an early immunoregulatory role of CD8<jats:sup>+<\/jats:sup> T\u2004cells.<\/jats:p>","DOI":"10.1002\/eji.200425074","type":"journal-article","created":{"date-parts":[[2004,9,22]],"date-time":"2004-09-22T13:04:47Z","timestamp":1095858287000},"page":"3091-3101","source":"Crossref","is-referenced-by-count":4,"title":["Reduced antigen concentration and costimulatory blockade increase IFN\u2010\u03b3 secretion in naive CD8<sup>+<\/sup> T\u2004cells"],"prefix":"10.1002","volume":"34","author":[{"given":"H\u00e5kan\u2004T.\u2004L.","family":"Hall","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Petrovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petter","family":"H\u00f6glund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,11]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.4049\/jimmunol.157.4.1350","article-title":"A direct role for IFN\u2010gamma in regulation of Th1 cell development.","volume":"157","author":"Bradley L. 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