{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:33:39Z","timestamp":1791214419321,"version":"4.1.0"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5934","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2009,6,19]]},"abstract":"Controlling Chronic Viral Infections<\/jats:title>\n \n Chronic viral infections such as HIV and hepatitis B and C viruses are major public health concerns. T cell\u2014mediated immune responses are critical for controlling viral infections. In contrast to acute infections, chronic viral infections are characterized by \u201cexhausted\u201d cytotoxic CD8\n +<\/jats:sup>\n T cells, cells which exhibit reduced proliferative capacity, cytokine secretion, and cytotoxicity. Treatments that reverse exhaustion result in increased viral control. Despite their exhaustion, these CD8\n +<\/jats:sup>\n T cells eventually help to control chronic infections by killing virally infected cells, and require CD4\n +<\/jats:sup>\n T cell help to do so. How do CD4\n +<\/jats:sup>\n T cells provide help to CD8\n +<\/jats:sup>\n T cells during chronic infection (see the Perspective by\n \n Johnson and Jameson<\/jats:related-article>\n <\/jats:bold>\n )?\n \n Elsaesser\n et al.<\/jats:italic>\n <\/jats:bold>\n (p.\n 1569<\/jats:related-article>\n , published online 7 May),\n \n Yi\n et al.<\/jats:italic>\n <\/jats:bold>\n (p.\n 1572<\/jats:related-article>\n , published online 14 May), and\n \n Fr\u00f6hlich\n et al.<\/jats:italic>\n <\/jats:bold>\n (p.\n 1576<\/jats:related-article>\n , published online 28 May) now show that the cytokine, interleukin-21 (IL-21), known to be critical for the differentiation of certain CD4\n +<\/jats:sup>\n T cell effector subsets, is an essential factor produced by CD4\n +<\/jats:sup>\n T cells that helps CD8\n +<\/jats:sup>\n T cells to control chronic lymphocytic choriomeningitis virus infection in mice. Acute and chronic infections resulted in differing amounts of IL-21 production by virus-specific CD4\n +<\/jats:sup>\n T cells. CD8\n +<\/jats:sup>\n T cells required IL-21 directly, and when CD8\n +<\/jats:sup>\n T cells were unable to signal through IL-21 or IL-21 was not available, they were reduced in number, exhibited a more exhausted phenotype, and were not able to control the virus. In contrast, the absence of IL-21\u2013dependent signaling did not affect primary CD8\n +<\/jats:sup>\n T cell responses to acute infection or responses to a viral rechallenge, suggesting that differentiation of memory CD8\n +<\/jats:sup>\n T cells is independent of IL-21.\n <\/jats:p>","DOI":"10.1126\/science.1175194","type":"journal-article","created":{"date-parts":[[2009,5,14]],"date-time":"2009-05-14T22:04:30Z","timestamp":1242338670000},"page":"1572-1576","source":"Crossref","is-referenced-by-count":450,"title":["A Vital Role for Interleukin-21 in the Control of a Chronic Viral Infection"],"prefix":"10.1126","volume":"324","author":[{"given":"John S.","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294\u20132170, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294\u20132170, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan J.","family":"Zajac","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294\u20132170, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/362758a0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.12.8056-8063.1994"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80628-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.9.1383"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2205"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.7.4204"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.16.10514-10527.2005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0703-861"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.7.4700-4704.1994"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.2.1072-1079.1996"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.23.12388-12393.2002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200208)32:8<2199::AID-IMMU2199>3.0.CO;2-L"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01441"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082305"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083317"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1129"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2834"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040504"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2007.04.003"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090316"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077002"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05970"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.03.003"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"e_1_3_2_28_2","unstructured":"M. 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