CD11b+ Migratory Dendritic Cells Mediate CD8 T Cell Cross-Priming and Cutaneous Imprinting after Topical Immunization

Nizza, Suzanne; Campbell, James J.

doi:10.1371/journal.pone.0091054

Cited by 16 publications

(13 citation statements)

References 39 publications

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“…This study suggests that local and systemic antitumor immunity may be differentially regulated, which is in line with our observations in relation to migratory versus LN-resident cDC subsets. Whereas LN-resident subsets appear to be vital for the generation of systemic immunity, providing protection against distant metastases, migratory subsets appear to direct local antitumor immunity, possibly through their ability to imprint and license primed effector T cells for selective homing to, and functional activity in, cutaneous compartments (40,41).…”

Section: Discussionmentioning

confidence: 99%

Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence

Hout

Koster

Sluijter

et al. 2017

Cancer Immunology Research

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Melanoma exerts immune-suppressive effects to facilitate tumor progression and metastatic spread. We studied these effects on dendritic cell (DC) and T-cell subsets in 36 melanoma sentinel lymph node (SLN) from 28 stage I-III melanoma patients and determined their clinical significance. Four conventional DC subsets, plasmacytoid DCs, and CD4, CD8, and regulatory T cells (Tregs), were analyzed by flow cytometry. We correlated these data to clinical parameters and determined their effect on local and distant melanoma recurrence, with a median follow-up of 75 months. In stage I and II melanoma, increased Breslow thickness (i.e., invasion depth of the primary melanoma) was associated with progressive suppression of skin-derived migratory CD1a DC subsets. In contrast, LN-resident DC subsets and T cells were only affected once metastasis to the SLN had occurred. In stage III patients, increased CD4:CD8 ratios in concert with the accumulation of Tregs resulted in decreased CD8:Treg ratios. On follow-up, lower frequencies of migratory DC subsets proved related to local melanoma recurrence, whereas reduced maturation of LN-resident DC subsets was associated with distant recurrence and melanoma-specific survival. In conclusion, melanoma-mediated suppression of migratory DC subsets in the SLN precedes local spread, whereas suppression of LN-resident DC subsets follows regional spread and precedes further melanoma dissemination to distant sites. This study offers a rationale to target migratory as well as LN-resident DC subsets for early immunotherapeutic interventions to prevent melanoma recurrence and spread. .

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Section: Discussionmentioning

confidence: 99%

Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence

Hout

Koster

Sluijter

et al. 2017

Cancer Immunology Research

View full text Add to dashboard Cite

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“…This has been observed predominantly, but not exclusively (169), in situations where inflammation is occurring, such as in viral and fungal infections, adjuvant injection, autoimmune tissue damage, and in response to cytokines (29, 170–173). The participation of other DCs in vivo has also been seen in situations where an exogenous antigen engages certain stimulatory cells receptors, such as the FcR or Dectin-1(171, 174).…”

Section: Types Of Antigen Presenting Cells That Cross-presentmentioning

confidence: 99%

The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules

Cruz

Colbert²,

Merino³

et al. 2017

Annu. Rev. Immunol.

232

228

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To monitor the health of cells, the immune system tasks antigen presenting cells with gathering antigens from other cells and reporting them to CD8 T cells in the form of peptides bound to MHC I molecules. Most cells would be unable to perform this function because they use their MHC I molecules to exclusively present peptides derived from the cell’s own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC I through a process called cross-presentation (XPT). How this important task is accomplished, its role in health and disease and its potential for exploitation are the subject of this review.

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“…LCs are characterized by the presence of an intracellular organelle called Birbeck granules (BG) and expresses high levels of its associated protein Langerin/CD207, a C-type lectin receptor that is responsible for the development of these granules [34]. While in some contexts LC have been ascribed with a suppressive role during contact sensitivity [35], dose and model dependent difference have also implicated LC in mediating inflammation [36] and LC have been implicated in transporting a model antigen like OVA to the skin draining LN for priming as well during tape stripping [37] Functional specialization of LC in mediating T cell priming in response to Candida albicans [38, 39]has been found to be specific only for T helper 17 (Th17) and not for CTLs (cytotoxic lymphocytes). Mouse and human LCs that constitute about 1-5% of the epidermal cell population also express E-cadherin (keratinocyte adhering molecule), CD205 and MHC-II molecules.…”

Section: Overview Of DC Subsets and Functional Specializationmentioning

confidence: 99%

The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Devi

Anandasabapathy

2016

Semin Immunopathol

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Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.

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CD11b+ Migratory Dendritic Cells Mediate CD8 T Cell Cross-Priming and Cutaneous Imprinting after Topical Immunization

Cited by 16 publications

References 39 publications

Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence

Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence

The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules

The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

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