{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:08:35Z","timestamp":1793873315911,"version":"4.6.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,9,10]]},"abstract":"<jats:p>\n                    Robust cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell response to the intracellular bacterium\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    . IRF4-deficient (\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>)<\/jats:italic>\n                    mice could not clear\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    infection and generated decreased numbers of\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    -specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells with impaired effector phenotype and function. Transfer of wild-type CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells into\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice improved bacterial clearance, suggesting an intrinsic defect of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Following transfer into wild-type recipients,\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells became activated and showed initial proliferation upon\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-\u03b3 and TNF-\u03b1, and failed to acquire cytotoxic function. Forced IRF4 expression in\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells rescued the defect. During acute infection,\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3,\n                    <jats:italic>Irf4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell differentiation, the identification of its decisive role in peripheral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1309378110","type":"journal-article","created":{"date-parts":[[2013,8,26]],"date-time":"2013-08-26T22:24:39Z","timestamp":1377555879000},"page":"15019-15024","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1073","volume":"110","author":[{"given":"Friederike","family":"Raczkowski","sequence":"first","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf, 20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Ritter","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, 35033 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Heesch","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf, 20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9a","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf, 20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Guralnik","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, 35033 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"H\u00f6cker","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, 35033 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmann","family":"Raifer","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, 35033 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bopp","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Harb","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg, 35043 Marburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f6rthe A.","family":"Kesper","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg, 35043 Marburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra I.","family":"Pfefferle","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg, 35043 Marburg, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Grusdat","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Willi","family":"Mittr\u00fccker","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf, 20246 Hamburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Huber","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, 35033 Marburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,8,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3307"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni802"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.017"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1268"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2153"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2158"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1403"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.06.021"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.014"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01113.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1500"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182425099"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011128"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.07.014"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.10.011"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205834109"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228309"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11531"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11530"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.016"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.18.2335"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5299.540"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205742109"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63681"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1461"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.11.010"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.10.008"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2006"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105133108"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1837"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.4.1528"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041204"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703510104"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939412"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","unstructured":"Brand S et al. 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