The Role of Skin-Derived Dendritic Cells in CD8+ T Cell Priming Following Immunization with Lentivectors

Furmanov, Karina; Elnekave, Mazal; Lehmann, Dan; Clausen, Björn E.; Kotton, Darrell N.; Hovav, Avi‐Hai

doi:10.4049/jimmunol.0903062

Cited by 32 publications

(33 citation statements)

References 38 publications

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“…Of note, it is unlikely to explain the unique role of buccal LCs simply by the differential repopulation kinetics of langerin + cells in the buccal versus skin. We clearly demonstrated the ablation of buccal mucosa LCs, but not Ln + iDCs, in mice treated with DT 7 d prior to immunization; these kinetics are identical to that observed in the skin as we recently published (40). Overall, our findings suggest that LCs in various tissues may have a different role in T cell priming even when an identical immunogen is used.…”

Section: Discussionsupporting

confidence: 84%

“…Our study suggests that organization of DCs in the oral mucosa (at least in the buccal mucosa and lining mucosa) is similar to the skin rather than to the vaginal mucosa. Indeed, we were able to identify three major DC subsets migrating from the buccal mucosa under inflammatory conditions that were similar to those migrating from the skin (40). To our knowledge, this work is the first to show the presence of Ln + iDCs in the buccal mucosa and lining mucosa.…”

Section: Discussionmentioning

confidence: 54%

“…Mice were i.p. administered DT (1 mg per mouse) 3 d before immunization and every 10 d thereafter to eliminate both LCs and Ln + iDCs as we previously reported for the skin model (40). This DT injection schedule led to a considerable decrease in the generation of SIINFEKL-specific CD8 + T cells in the blood of buccally immunized mice but not in lining-immunized mice (Fig.…”

Section: Different Function For Buccal and Lining Langerin + Dcs In Tmentioning

confidence: 69%

“…Lang-DTR mice were treated with a single dose of DT 7 d before immunization (Fig. 5B), a strategy previously reported to deplete skin LCs but not Ln + dDCs at the time of immunization (40). To confirm this approach for the buccal mucosa, we painted the buccal mucosa of mice with FITC/DBP solution and treated them with either a single injection of DT or with repeated DT injections.…”

Section: Different Function For Buccal and Lining Langerin + Dcs In Tmentioning

confidence: 95%

“…Three days later, the cervical LNs were collected, processed, and CD11c + cells were enriched by magnetic bead-based positive selection. The cells were then stained with anti-CD11c, CD103, and Ep-CAM Abs to identify the various oral DC subsets based on their phenotype in the skin as previously described (23,40) Fig. 4A, buccal and lining migratory DCs were easily identified in the cervical LNs by FITC painting, whereas no FITC + cells were found in unpainted mice.…”

Section: Migration Of Oral Dcs Under Inflammatory Conditionsmentioning

confidence: 99%

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Dendritic Cells in Distinct Oral Mucosal Tissues Engage Different Mechanisms To Prime CD8+ T Cells

Nudel

Elnekave

Furmanov

et al. 2011

The Journal of Immunology

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Although oral dendritic cells (DCs) were shown to induce cell-mediated immunity, the identity and function of the various oral DC subsets involved in this process is unclear. In this study, we examined the mechanisms used by DCs of the buccal mucosa and of the lining mucosa to elicit immunity. After plasmid DNA immunization, buccally immunized mice generated robust local and systemic CD8+ T cell responses, whereas lower responses were seen by lining immunization. A delayed Ag presentation was monitored in vivo in both groups; yet, a more efficient presentation was mediated by buccal-derived DCs. Restricting transgene expression to CD11c+ cells resulted in diminished CD8+ T cell responses in both oral tissues, suggesting that immune induction is mediated mainly by cross-presentation. We then identified, in addition to the previously characterized Langerhans cells (LCs) and interstitial dendritic cells (iDCs), a third DC subset expressing the CD103+ molecule, which represents an uncharacterized subset of oral iDCs expressing the langerin receptor (Ln+iDCs). Using Langerin-DTR mice, we demonstrated that whereas LCs and Ln+iDCs were dispensable for T cell induction in lining-immunized mice, LCs were essential for optimal CD8+ T cell priming in the buccal mucosa. Buccal LCs, however, failed to directly present Ag to CD8+ T cells, an activity that was mediated by buccal iDCs and Ln+iDCs. Taken together, our findings suggest that the mechanisms engaged by oral DCs to prime T cells vary between oral mucosal tissues, thus emphasizing the complexity of the oral immune network. Furthermore, we found a novel regulatory role for buccal LCs in potentiating CD8+ T cell responses.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 54%

Section: Different Function For Buccal and Lining Langerin + Dcs In Tmentioning

confidence: 69%

Section: Different Function For Buccal and Lining Langerin + Dcs In Tmentioning

confidence: 95%

Section: Migration Of Oral Dcs Under Inflammatory Conditionsmentioning

confidence: 99%

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Dendritic Cells in Distinct Oral Mucosal Tissues Engage Different Mechanisms To Prime CD8+ T Cells

Nudel

Elnekave

Furmanov

et al. 2011

The Journal of Immunology

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Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice

et al. 2016

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Uptake of biodegradable poly(γ-glutamic acid) nanoparticles and antigen presentation by dendritic cells in vivo

Uto

Toyama

Nishi

et al. 2013

Results in Immunology

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Poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) carrying antigens have been shown to induce potent antigen-specific immune responses. However, in vivo delivery of γ-PGA NPs to dendritic cells (DCs), a key regulator of immune responses, still remains unclear. In this study, γ-PGA NPs were examined for their uptake by DCs and subsequent migration from the skin to the regional lymph nodes (LNs) in mice. After subcutaneous injection of fluorescein 5-isothiocyanate (FITC)-labeled NPs or FITC-ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs), DCs migrated from the skin to the LNs and maturated, resulting in the upregulation of the costimulatory molecules CD80 and CD86 and the chemokine receptor CCR7. However, the migrated DCs were not detected in the spleen. FITC-OVA-NPs were found to be taken up by skin-derived CD103(+) DCs, and the processed antigen peptides were cross-presented by the major histocompatibility complex (MHC) class I molecule of DCs. Furthermore, significant activation of antigen-specific CD8(+) T cells was observed in mice immunized with OVA-carrying NPs (OVA-NPs) but not with OVA alone or OVA with an aluminum adjuvant. The antigen-specific CD8(+) T cells were induced within 7 days after immunization with OVA-NPs. Thus, γ-PGA NPs carrying various antigens may have great potential as an antigen-delivery system and vaccine adjuvant in vivo.

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The Role of Skin-Derived Dendritic Cells in CD8+ T Cell Priming Following Immunization with Lentivectors

Abstract: Material

Cited by 32 publications

References 38 publications

Dendritic Cells in Distinct Oral Mucosal Tissues Engage Different Mechanisms To Prime CD8+ T Cells

Dendritic Cells in Distinct Oral Mucosal Tissues Engage Different Mechanisms To Prime CD8+ T Cells

Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice

Uptake of biodegradable poly(γ-glutamic acid) nanoparticles and antigen presentation by dendritic cells in vivo

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