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Using a mouse model mimicking acute HBV infection by hydrodynamic injection of an HBV plasmid, we observed that although serum hepatitis B surface Ag and hepatitis B envelope Ag were eliminated within 3 to 4 wk, HBV might persist for &amp;gt;8 wk in CD8\u2212\/\u2212 mice and that adoptive transfer of anti-HBV CD8+ T cells restored the ability to clear HBV in HBV-carrier Rag1\u2212\/\u2212 mice. These results indicate that CD8+ T cells are critical in HBV elimination. Furthermore, NK cells increased IFN-\u03b3 production after HBV plasmid injection, and NK cell depletion led to significantly increased HBV persistence along with reduced frequency of hepatitis B core Ag\u2013specific CD8+ T cells. Adoptive transfer of IFN-\u03b3\u2013sufficient NK cells restored donor CD8+ T cell function, indicating that NK cells positively regulated CD8+ T cells via secreting IFN-\u03b3. We also observed that NK cell depletion correlated with decreased effector memory CD8+ T cell frequencies. Importantly, adoptive transfer experiments showed that NK cells were involved in anti-HBV CD8+ T cell recall responses. Moreover, DX5+CD49a\u2212 conventional, but not DX5\u2212CD49a+ liver-resident, NK cells were involved in improving CD8+ T cell responses against HBV. Overall, the current study reveals that NK cells, especially DX5+CD49a\u2212 conventional NK cells, promote the antiviral activity of CD8+ T cell responses via secreting IFN-\u03b3 in a mouse model mimicking acute HBV infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1500846","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T05:41:12Z","timestamp":1461217272000},"page":"4122-4131","source":"Crossref","is-referenced-by-count":58,"title":["NK Cells Help Induce Anti\u2013Hepatitis B Virus CD8+ T Cell Immunity in Mice"],"prefix":"10.1093","volume":"196","author":[{"given":"Meijuan","family":"Zheng","sequence":"first","affiliation":[{"name":"Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027 ,","place":["China"]},{"name":"Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230022 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027 ,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang 310003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,5,15]]},"reference":[{"key":"2025030702170092000_r1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.1198687","article-title":"Innate or adaptive immunity? 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