title: Impaired dendritic cell functions because of depletion of natural killer cells disrupt antigen-specific immune responses in mice: restoration of adaptive immunity in natural killer-depleted mice by antigen-pulsed dendritic cell.
abstract: The primary aim of this study was to evaluate the role of natural killer (NK) cells on antigen-specific adaptive immune responses. After analysing the mechanism of impaired adaptive immune responses of NK-depleted mice, an immune interventional approach was developed to restore adaptive immunity in NK-depleted mice. NK cells were depleted from mice by administration of anti-asialo GM1 antibody (100 mul/mouse), twice, at an interval of 48 h. Hepatitis B surface antigen (HBsAg) was administered intraperitoneally to normal C57BL/6 mice (control mice) and NK-depleted mice. The levels of antibody to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen were assessed. The functions of T lymphocytes, B lymphocytes and dendritic cells (DCs) were evaluated in vitro. HBsAg-pulsed DCs were prepared by culturing spleen DCs with HBsAg for 48 h and administered once to NK-depleted mice. The levels of anti-HBs in the sera and HBsAg-specific lymphocytes were significantly lower in NK-depleted mice compared with control mice (P < 0.05). The functions of T and B lymphocytes were similar between control mice and NK-depleted mice. However, the functions of spleen DC and liver DC were significantly lower in NK-depleted mice compared with control mice (P < 0.05). Administration of HBsAg-pulsed DCs, but not HBsAg, induced HBsAg-specific humoral and cellular immune responses in NK-depleted mice. Our study suggests that cross-talk between NK cells and DCs regulates the magnitude of adaptive immunity. In addition, antigen-pulsed immunogenic DCs represent potent immune modulator even if subjects with diminished innate immunity.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Yoshida
authors.forename: F
authors.initials: F
authors.lastname: Akbar
authors.forename: T
authors.initials: T
authors.lastname: Miyake
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: B
authors.initials: B
authors.lastname: Matsuura
authors.forename: Y
authors.initials: Y
authors.lastname: Hiasa
authors.forename: M
authors.initials: M
authors.lastname: Onji
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation / Q000276:immunology; D018845:CD11 Antigens / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D018845:CD11 Antigens; D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside