title: NK Cells Help Induce Anti-Hepatitis B Virus CD8+ T Cell Immunity in Mice.
abstract: Although recent clinical studies demonstrate that NK cell function is impaired in hepatitis B virus (HBV)-persistent patients, whether or how NK cells play a role in anti-HBV adaptive immunity remains to be explored. 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 >8 wk in CD8(-/-) mice and that adoptive transfer of anti-HBV CD8(+) T cells restored the ability to clear HBV in HBV-carrier Rag1(-/-) mice. These results indicate that CD8(+) T cells are critical in HBV elimination. Furthermore, NK cells increased IFN-γ production after HBV plasmid injection, and NK cell depletion led to significantly increased HBV persistence along with reduced frequency of hepatitis B core Ag-specific CD8(+) T cells. Adoptive transfer of IFN-γ-sufficient NK cells restored donor CD8(+) T cell function, indicating that NK cells positively regulated CD8(+) T cells via secreting IFN-γ. 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(-) conventional, but not DX5(-)CD49a(+) 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(-) conventional NK cells, promote the antiviral activity of CD8(+) T cell responses via secreting IFN-γ in a mouse model mimicking acute HBV infection.
authors.affiliation: 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, China; Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; and.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zheng
authors.affiliation: 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, China; tzg@ustc.edu.cn sunr@ustc.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: 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, China;
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.affiliation: 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, China; 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, China tzg@ustc.edu.cn sunr@ustc.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000235:genetics; D014759:Viral Envelope Proteins / Q000276:immunology; D019562:Viral Load; D000098815:T-bet Transcription Factor
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D006514:Hepatitis B Surface Antigens; D018398:Homeodomain Proteins; C497441:Nfil3 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014759:Viral Envelope Proteins; C064658:RAG-1 protein; D007371:Interferon-gamma