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.

Nishimura T, Kitamura H, Iwakabe K, Yahata T, Ohta A, Sato M, Takeda K, Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nakui M, Sekimoto M, Koda T
Int Immunol. 2000 12 (7): 987-94

PMID: 10882410 · DOI:10.1093/intimm/12.7.987

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.

MeSH Terms (19)

Adjuvants, Immunologic Animals Antigen Presentation Antigens, CD Antigens, CD1 Antigens, CD1d Antigens, Differentiation, T-Lymphocyte CD40 Antigens CD40 Ligand Cell Differentiation Dendritic Cells Galactosylceramides Interferon-gamma Killer Cells, Natural Lectins, C-Type Membrane Glycoproteins Mice Mice, Inbred C57BL T-Lymphocytes, Cytotoxic

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