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, Takashi; Kitamura, Hiroyuki; Iwakabe, Kenji; Yahata, Takashi; Ohta, Akio; Sato, Masamitsu; Takeda, Kazuyoshi; Okumura, Ko; Kaer, Luc Van; Kawano, Tetsu; Taniguchi, Masaru; Nakui, Minoru; Sekimoto, Miho; Koda, Toshiaki

doi:10.1093/intimm/12.7.987

Cited by 203 publications

(176 citation statements)

References 32 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…This activity is thought to arise through iNKT cell-mediated activation of NK cells and rapid induction of IFN-␥ (43), with the antiangiogenic property of IFN-␥ playing a key role (44). It has been reported that some antitumor CTL activity may also be invoked through iNKT activation with ␣-GalCer (45,46). Our results would suggest that this activity would be dependent upon iNKT-mediated activation of DC that have acquired unique tumor Ags.…”

Section: Discussionmentioning

confidence: 52%

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

Hermans

Silk

Gileadi

et al. 2003

The Journal of Immunology

448

445

View full text Add to dashboard Cite

Modification in the function of dendritic cells (DC), such as that achieved by microbial stimuli or T cell help, plays a critical role in determining the quality and size of adaptive responses to Ag. NKT cells bearing an invariant TCR (iNKT cells) restricted by nonpolymorphic CD1d molecules may constitute a readily available source of help for DC. We therefore examined T cell responses to i.v. injection of soluble Ag in the presence or the absence of iNKT cell stimulation with the CD1d-binding glycolipid α-galactosylceramide (α-GalCer). Considerably enhanced CD4+ and CD8+ T cell responses were observed when α-GalCer was administered at the same time as or close to OVA injection. This enhancement was dependent on the involvement of iNKT cells and CD1d molecules and required CD40 signaling. Studies in IFN-γR−/− mice indicated that IFN-γ was not required for the adjuvant effect of α-GalCer. Consistent with this result, enhanced T cell responses were observed using OCH, an analog of α-GalCer with a truncated sphingosine chain and a reduced capacity to induce IFN-γ. Splenic DC from α-GalCer-treated animals expressed high levels of costimulatory molecules, suggesting maturation in response to iNKT cell activation. Furthermore, studies with cultured DC indicated that potentiation of T cell responses required presentation of specific peptide and α-GalCer by the same DC, implying conditioning of DC by iNKT cells. The iNKT-enhanced T cell responses resisted challenge with OVA-expressing tumors, whereas responses induced in the absence of iNKT stimulation did not. Thus, iNKT cells exert a significant influence on the efficacy of immune responses to soluble Ag by modulating DC function.

show abstract

Section: Discussionmentioning

confidence: 52%

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

Hermans

Silk

Gileadi

et al. 2003

The Journal of Immunology

448

445

View full text Add to dashboard Cite

show abstract

“…41,45,49,54 -56,58,61 By responding to infectious or other challenges prior to conventional adaptive T cells, CD1d-reactive T cells could have the potential to influence the course of local and systemic bias of immune responses. Activated CD1d-reactive T cells can stimulate NK cells 59 and cytotoxic T lymphocytes, 23,24,62 actions dependent in part on the ability of the CD1d-reactive T cells to produce IFN-␥. In addition to the possible role of CD1d-reactive T-cell-produced cytokines as facilitators of immune responses, IFN-␥ and other cytokines may play a role in the clearance of pathogens, especially viral pathogens.…”

Section: Roles Of Cd1d-reactive Nkt Cellsmentioning

confidence: 99%

To be or not to be NKT: Natural killer T cells in the liver

2004

View full text Add to dashboard Cite

N KT cells are a diverse group of cells that share features of both classical T cells and natural killer (NK) cells, and have similarly diverse functions. One of the complexities in understanding NKT cells involves sorting through the various terminology that has been applied to them in the emerging literature. 1,2 Functionally, a major subset of these cells are defined by reactivity against CD1d, which is one of five known glycolipid-binding nonpolymorphic major histocompatibility complex class 1-like glycoproteins: CD1a through e. 3 These glycoproteins appear to have evolved to facilitate recognition of nonprotein antigens-specifically glycolipid antigens, including those present in the cell walls of mycobacterial species. CD1d is constitutively expressed on a number of hematopoietic-derived antigenpresenting cell (APC) types-including B cells and myeloid cells-and can be expressed by human T cells as well as healthy hepatocytes. Physiological ligands for CD1d remain poorly defined, although both glycolipids and hydrophobic peptides bind to CD1 family molecules. 4,5 Most antigen studies have used the synthetic glycolipid ␣-galactosylceramide (␣GalCer), which binds to CD1d and activates a specific subset of both murine and human NKT cells in vitro and in vivo. 5,6 CD1d is remarkably conserved across mammalian species, with mouse and human CD1d having greater than 90% sequence homology. 7 Consequently, murine CD1d-reactive T cells recognize human CD1d, and vice versa. 8 After activation, NKT cells are highly versatile and can produce large amounts of interferon gamma (IFN-␥) and interleukin (IL)-4 9,10 as prototypic type 1 and type 2 cytokines, respectively, as well as display NK/lymphokine-activated killing-like FasL-mediated or perforin-dependent CD1d-specific cytotoxicity 11-14 thus potentially contributing to protective and pathogenic responses against multiple infectious agents and tumors.CD1d is expressed by dendritic cells (DCs), and ␣Gal-Cer-loaded DCs mediate activation of invariant NKT cells. [15][16][17][18] Although peripheral NKT cells can recognize and respond to other CD1d ϩ cells, their in vivo activation may be initiated by interactions with DCs and possibly B cells. The interactions between invariant NKT cells and DCs share many features of interactions between conventional CD4 ϩ T cells and DCs. DCs pulsed with ␣GalCer stimulate NKT cells through T cell receptor (TCR) ligation. 2,19,20 NKT cell activation and IFN-␥ production are markedly enhanced by DC-produced IL-12, with an increase in the IL-12 receptor on activated NKT cells. 15,21,22 Conversely, invariant NKT cells also interact with ␣Gal-Cer-loaded DCs to enhance CD4 ϩ and CD8 ϩ T-cell responses 16,17,23,24 and with B cells to provide help for antibody production. 25 However, ␣Galcer is not a physiological antigen, and it is not yet clear whether physiological NKT-DC interactions are mediated by specific CD1d-presented antigens or are antigen independent.The classical CD1d-reactive NKT cell population expresses a highly restricted TCR r...

show abstract

“…Data from many groups indicate that iNKT functions can be mediated through interactions with CD1d ϩ APC including DCs and B cells (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Murine studies have shown that iNKT activation can be enhanced by B7 ligation of CD28 and that IL-12 produced by DCs can further enhance iNKT IFN␥ production (11,12,20).…”

mentioning

confidence: 99%

CD1d ligation on human monocytes directly signals rapid NF-κB activation and production of bioactive IL-12

Yue

Shaulov

Wang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Natural killer T cells (NKT cells) expressing a semiinvariant CD1d-reactive T cell receptor (invariant NKT, iNKT) can be rapidly activated by monocytes or immature dendritic cells (iDCs) bearing aCD1d-presented glycolipid antigen and can in turn stimulate these myeloid cells to mature and produce IL-12. Previous studies have shown that iNKT-produced IFN␥ and CD40 ligand contribute to this dendritic cell maturation. This study demonstrates that CD1d ligation alone, in the absence of iNKT, could rapidly (within 24 h) stimulate production of bioactive IL-12p70 by CD1d ؉ human peripheral blood monocytes as well as iDCs. IFN␥ alone had no effect, but it markedly enhanced CD1d-stimulated IL-12 production. Monocyte differentiation, as assessed by CD40 and CD1a upregulation, was also accelerated by CD1d stimulation, consistent with this representing a physiological response. CD1d ligation on the human monocytic cell line THP-1 similarly specifically stimulated IL-12 production. Biochemical studies showed that IL-12 release correlated with rapid phosphorylation of I B, a critical step in NF-B activation. Selective NF-B inhibition blocked this CD1d-stimulated IL-12 production. Finally, CD1d ligation could also enhance IL-12 production in the presence of suboptimal LPS or CD40 stimulation. These findings demonstrate an innate immune signaling function for CD1d and provide a mechanism for the rapid activation of monocytes and iDCs by CD1d-reactive T cells.antigen-presenting cell ͉ innate immunity ͉ natural killer T cell C D1d is a nonpolymorphic MHC class I-like protein constitutively expressed by antigen-presenting cells (APC) and by some epithelia, whereas CD1a-c are induced upon dendritic cell (DC) maturation. CD1d is recognized by a subpopulation of T cells, many of which express markers typical of natural killer cells and have been termed natural killer T cells (NKT cells) (1-3). A major fraction of CD1d-restricted T cells recognize CD1d through an invariant T cell receptor (TCR)␣ chain (V␣24-J␣18 in humans). CD1d-reactive NKT cells using this invariant TCR (iNKT) are largely primed in vivo for the rapid production of T helper 1 and T helper 2 cytokines (IFN␥ and IL-4) and have regulatory functions in innate and adaptive immune responses (3, 4). A glycolipid antigen isolated from marine sponge (␣-galactosylceramide, ␣galcer) is recognized by iNKT in the context of CD1d (5-8). In vivo, ␣galcer causes activation of iNKT, rapid cytokine production, and subsequent systemic activation of innate and adaptive immune cells (9, 10).Data from many groups indicate that iNKT functions can be mediated through interactions with CD1d ϩ APC including . Murine studies have shown that iNKT activation can be enhanced by B7 ligation of CD28 and that IL-12 produced by DCs can further enhance iNKT IFN␥ production (11,12,20). Conversely, murine and human studies have shown that iNKT can stimulate the maturation of ␣galcer-pulsed DCs (11,12,18,20). This DC stimulation appears to be mediated by CD40 ligand on the iNKT through ligation of CD40 ...

show abstract

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

Cited by 203 publications

References 32 publications

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells

To be or not to be NKT: Natural killer T cells in the liver

CD1d ligation on human monocytes directly signals rapid NF-κB activation and production of bioactive IL-12

Contact Info

Product

Resources

About