title: The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes.
abstract: In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of alpha-GalCer resulted in the induction of the early activation marker CD69 on CD4(+) T cells, CD8(+) T cells and B cells in addition to macrophages and NKT cells. However, no significant induction of CD69 was observed on cells from CD1d- or V(alpha)14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to alpha-GalCer. Indeed, in vivo injection of alpha-GalCer resulted not only in the activation of NKT cells but also in the generation of CD69(+)CD8(+) T cells possessing both cytotoxic T lymphocyte (CTL) activity and IFN-gamma-producing ability. Tumor-specific CTL generation was also accelerated by alpha-GalCer. The critical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC interaction during the development of CD69(+)CD8(+) CTL by alpha-GalCer was demonstrated by blocking experiments using anti-CD40L mAb. These findings provide direct evidence for a critical role of CD1d-restricted NKT cells and DC in bridging innate and acquired immunity.
authors.affiliation: Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Iwakabe
authors.forename: T
authors.initials: T
authors.lastname: Yahata
authors.forename: A
authors.initials: A
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: L
authors.initials: L
authors.lastname: Van Kaer
authors.forename: T
authors.initials: T
authors.lastname: Kawano
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: M
authors.initials: M
authors.lastname: Nakui
authors.forename: M
authors.initials: M
authors.lastname: Sekimoto
authors.forename: T
authors.initials: T
authors.lastname: Koda
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis*; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000502:physiology*; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D000099192:CD69 Antigens
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D023201:CD40 Ligand; D005699:Galactosylceramides; D007371:Interferon-gamma; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D000099192:CD69 Antigens