title: NKT cells determine titer and subtype profile of virus-specific IgG antibodies during herpes simplex virus Infection.
abstract: Invariant NKT cells (iNKT cells) are innate lymphocytes that recognize lipid-derived Ags presented by the MHC class I-related protein CD1d. In this study, we analyzed the role of iNKT cells in the generation of Abs against HSV type 1 (HSV-1). In sera from healthy hman donors, we found a correlation between HSV-1-specific IgG titers and proportions of CD4(+) iNKT cells. In HSV-1-infected iNKT cell-deficient mice, the amount of specific IgM and IgG Abs were significantly reduced compared with wild-type mice. Moreover, iNKT cell-deficient mice were unable to upregulate CD1d on B cells and failed to establish an IFN-γ-driven subtype profile of HSV-1-specific IgG Abs. In spleens of HSV-1-infected wild-type mice, the percentage of iNKT cells expressing CCR6, a marker for inflammatory iNKT cells secreting IFN-γ, was significantly decreased at 6 mo postinfection, suggesting that these cells were released from the spleen to other tissues. Finally, in vitro experiments showed that in the absence of CD1d-restricted cells, HSV-1 induced markedly lower IFN-γ production in splenocytes from naive mice. Taken together, our results indicate that iNKT cells shape the Ab response to HSV-1 infection and provide a basis for rational development of antiviral vaccines.
authors.affiliation: Institut für Virologie, Helmut-Ruska-Haus, Charité - Universitätsmedizin Berlin, 10117 Berlin, Gemany;
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Eike
authors.initials: E
authors.lastname: Wolter
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
authors.forename: Helga
authors.initials: H
authors.lastname: Meisel
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Günther
authors.initials: G
authors.lastname: Schönrich
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G