Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction

Shimizu, Kazuo; Asakura, Miki; Shinga, Jun; Sato, Yusuke; Kitahara, Shuji; Hoshino, Katsuaki; Kaisho, Tsuneyasu; Schoenberger, Stephen P.; Ezaki, Taichi; Fujii, Shin‐ichiro

doi:10.4049/jimmunol.1300033

Cited by 42 publications

(44 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was shown that NKT cells can interact via OX40/OX40L with pDCs, which then contribute to the activation of conventional DCs for T cell priming (33,34). Because pDCs are a major producer of type I IFN (35), we assessed whether this cytokine contributed to the NKT cell-mediated conditioning observed in the previous experiments.…”

Section: Activated Nkt Cells Condition Different DC Subsets To Responmentioning

confidence: 98%

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Osmond

Farrand

Painter

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

The function of dendritic cells (DCs) can be modulated through multiple signals, including recognition of pathogen-associated molecular patterns, as well as signals provided by rapidly activated leukocytes in the local environment, such as innate-like T cells. In this article, we addressed the possibility that the roles of different murine DC subsets in cross-priming CD8+ T cells can change with the nature and timing of activatory stimuli. We show that CD8α+ DCs play a critical role in cross-priming CD8+ T cell responses to circulating proteins that enter the spleen in close temporal association with ligands for TLRs and/or compounds that activate NKT cells. However, if NKT cells are activated first, then CD8α− DCs become conditioned to respond more vigorously to TLR ligation, and if triggered directly, these cells can also contribute to priming of CD8+ T cell responses. In fact, the initial activation of NKT cells can condition multiple DC subsets to respond more effectively to TLR ligation, with plasmacytoid DCs making more IFN-α and both CD8α+ and CD8α− DCs manufacturing more IL-12. These results suggest that different DC subsets can contribute to T cell priming if provided appropriately phased activatory stimuli, an observation that could be factored into the design of more effective vaccines.

show abstract

Section: Activated Nkt Cells Condition Different DC Subsets To Responmentioning

confidence: 98%

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Osmond

Farrand

Painter

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…(B) The absolute numbers of three MDSC subsets in the spleen from mice groups described in (A) were quantified after gating based on the expression levels of Gr1 and CD11b (n D 4-6, mean § SEM; *p < 0.05 for non-vs. anti-NK1.1). (C) NK cells were directly isolated from spleen of Rag1 ¡/¡ mice using anti-DX5 Ab-conjugated bead were cocultured with CD11b C Gr1 C MDSCs at a 1:1 ratio for 6 h. CD107 expression was analyzed using Alexa488-CD107a and IFNg production by intracellular staining as previously described 53 . (n D 4, mean § SEM; IFNg; *p < 0.05 for -MDSC vs. CMDSC in R2, CD107a; *p < 0.05 -MDSC vs. CMDSC in R1, R2, and R3) (D) NK cell cytotoxicity against each MDSC subset was determined as described in Methods (n D 4, mean § SEM; *p < 0.05 for Ly6G hi Ly6C med vs. Ly6G med Ly6C hi , and Ly6G hi Ly6C med vs. Ly6G med Ly6C med ).…”

Section: E995541-4mentioning

confidence: 99%

Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

et al. 2015

Self Cite

View full text Add to dashboard Cite

TNFa, tumor necrosis factor a; VEGF, vascular endothelial growth factor.Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1 C CD11b C Ly6G med Ly6C med MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27 C CD11b C NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14 C HLA-DR ¡ and CD14 ¡ HLA-DR ¡ MDSC) in NHL patients and found that higher IL-10-producing CD14 C HLA-DR ¡ MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.

show abstract

“…Using two different tumor models, our data reveal that a-GalCer/ Ag codelivery to CD8a + DCs triggers antitumor responses, in prophylactic and/or therapeutic settings. Of interest, Shimizu and colleagues (22,23) showed that inoculation of irradiated tumor cells previously loaded with a-GalCer promotes antitumor immunity through Ag cross-presentation and CTL responses. In this setting, dying tumor cells are selectively taken up by CD8a + DCs, and the subsequent cross-presentation of a-GalCer to NKT cells and tumor Ags to CD8 + T cells leads to strong and long-lasting antitumor responses (22).…”

Section: Nps Incorporating A-galcer and Ag Protect Against Tumor Devementioning

confidence: 99%

“…Of interest, Shimizu and colleagues (22,23) showed that inoculation of irradiated tumor cells previously loaded with a-GalCer promotes antitumor immunity through Ag cross-presentation and CTL responses. In this setting, dying tumor cells are selectively taken up by CD8a + DCs, and the subsequent cross-presentation of a-GalCer to NKT cells and tumor Ags to CD8 + T cells leads to strong and long-lasting antitumor responses (22). Using a different strategy (DC targeting by means of a synthetic vector), our data are in line with the concept that having both tumor Ag and a-GalCer on the same cell resulted in more efficient cross-presentation of Ag to CD8 + T cells.…”

Section: Nps Incorporating A-galcer and Ag Protect Against Tumor Devementioning

confidence: 99%

“…For instance, administration of a-GalCer-loaded DCs is more potent than a-GalCer alone in both preclinical and clinical tumor studies (18,20,21). Finally, simultaneous presentation of a-GalCer and tumor Ag by DCs optimizes CTL-mediated antitumor responses (22,23). Although promising, the transfer of autologous a-GalCer-loaded DCs applied to clinics represents a relatively invasive and costly procedure (6).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Targeted Delivery of α-Galactosylceramide to CD8α+ Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses

Macho-Fernandez

Cruz

Ghinnagow

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Immunotherapy aiming at enhancing innate and acquired host immunity is a promising approach for cancer treatment. The invariant NKT (iNKT) cell ligand α-galactosylceramide (α-GalCer) holds great promise in cancer therapy, although several concerns limit its use in clinics, including the uncontrolled response it promotes when delivered in a nonvectorized form. Therefore, development of delivery systems to in vivo target immune cells might be a valuable option to optimize iNKT cell–based antitumor responses. Using dendritic cell (DC)–depleted mice, DC transfer experiments, and in vivo active cell targeting, we show that presentation of α-GalCer by DCs not only triggers optimal primary iNKT cell stimulation, but also maintains secondary iNKT cell activation after challenge. Furthermore, targeted delivery of α-GalCer to CD8α+ DCs, by means of anti-DEC205 decorated nanoparticles, enhances iNKT cell–based transactivation of NK cells, DCs, and γδ T cells. We report that codelivery of α-GalCer and protein Ag to CD8α+ DCs triggers optimal Ag-specific Ab and cytotoxic CD8+ T cell responses. Finally, we show that targeting nanoparticles containing α-GalCer and Ag to CD8α+ DCs promotes potent antitumor responses, both in prophylactic and in therapeutic settings. Our data may have important implications in tumor immunotherapy and vaccine development.

show abstract

Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction

Cited by 42 publications

References 54 publications

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

Targeted Delivery of α-Galactosylceramide to CD8α+ Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses

Contact Info

Product

Resources

About