{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:41:19Z","timestamp":1792676479125,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD4 T cells have been shown to be necessary for the prevention of encephalitis during West Nile virus (WNV) infection. However, the mechanisms used by Ag-specific CD4 T cells to protect mice from WNV encephalitis remain incompletely understood. Contrary to the belief that CD4 T cells are protective because they merely maintain the CD8 T cell response and improve Ab production, in this study we provide evidence for the direct antiviral activity of CD4 T cells that functions to protect the host from WNV encephalitis. In adoptive transfers, naive CD4 T cells protected a significant number of lethally infected RAG\u2212\/\u2212 mice, demonstrating the protective effect of CD4 T cells independent of B cells and CD8 T cells. To shed light on the mechanism of this protection, we defined the peptide specificities of the CD4 T cells responding to WNV infection in C57BL\/6 (H-2b) mice, and used these peptides to characterize the in vivo function of antiviral CD4 T cells. WNV-specific CD4 T cells produced IFN-\u03b3 and IL-2, but also showed potential for in vivo and ex vivo cytotoxicity. Furthermore, peptide vaccination using CD4 epitopes conferred protection against lethal WNV infection in immunocompetent mice. These results demonstrate the role of direct effector function of Ag-specific CD4 T cells in preventing severe WNV disease.<\/jats:p>","DOI":"10.4049\/jimmunol.181.12.8568","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:24:21Z","timestamp":1397849061000},"page":"8568-8575","source":"Crossref","is-referenced-by-count":146,"title":["West Nile Virus-Specific CD4 T Cells Exhibit Direct Antiviral Cytokine Secretion and Cytotoxicity and Are Sufficient for Antiviral Protection"],"prefix":"10.1093","volume":"181","author":[{"given":"James D","family":"Brien","sequence":"first","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Department of Molecular Microbiology and Immunology, and Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Uhrlaub","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Department of Molecular Microbiology and Immunology, and Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Department of Immunobiology and Arizona Center on Aging, University of Arizona College of Medicine , Tucson, AZ 85718"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janko","family":"Nikolich-\u017dugich","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Department of Molecular Microbiology and Immunology, and Oregon National Primate Research Center, Oregon Health and Science University , Beaverton, OR 97006"},{"name":"Department of Immunobiology and Arizona Center on Aging, University of Arizona College of Medicine , Tucson, AZ 85718"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,12,15]]},"reference":[{"key":"2025032719415693500_R1","first-page":"2331","article-title":"Isolation of West Nile virus from mosquitoes, crows, and a Cooper\u2019s hawk in Connecticut","volume-title":"Science","year":"1999"},{"key":"2025032719415693500_R2","first-page":"2333","article-title":"Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States","volume-title":"Science","year":"1999"},{"key":"2025032719415693500_R3","first-page":"1204","article-title":"West Nile virus activity: United States, January 1-November 7, 2006","volume-title":"Morbid. 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