Antigen Crosspresentation by Human Plasmacytoid Dendritic Cells

Hoeffel, Guillaume; Ripoche, Anne-Claire; Matheoud, Diana; Nascimbeni, Michelina; Escriou, Nicolas; Lebon, Pierre; Heshmati, Farhad; Guillet, Jean‐Gérard; Gannagé, Monique; Caillat‐Zucman, Sophie; Casartelli, Nicoletta; Schwartz, Olivier; Hanau, Daniel; Hosmalin, Anne; Maranon, Concepciion

doi:10.1016/j.immuni.2007.07.021

Cited by 233 publications

(218 citation statements)

References 61 publications

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Section: Discussionmentioning

confidence: 99%

“…Currently we are exploring the potential involvement of plasmacytoid DC in the residual presentation because these are not depleted in the CD11cDTR-GFP transgenic system (data not shown). The function of plasmacytoid DC in antigen crosspresentation to CD8 1 T cells has been recently reported [54].The role of DC in tumor immunotherapy based on anti-CD137 mAb was found to be more dispensable than anticipated. Removal of DC clearly reduces the level of CTL stimulation achieved, but residual mechanisms under artificial costimulation through CD137 mAb are still capable of inducing tumor rejection with certain delay in a number of cases.…”

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confidence: 89%

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In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

et al. 2009

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Anti-CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti-tumor effect involves costimulation of tumor-specific CD8 1 T cells. Whether antigen cross-presenting DC are required for the efficacy of anti-CD137 mAb treatment has never been examined. Here we show that the administration of anti-CD137 mAb eradicates EG7-OVA tumors by a strictly CD8b 1 T-celldependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen crosspresentation revealed that CD11c 1 cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumordraining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti-OVA CTL induction. Using CD11c diphtheria toxin receptor-green fluorescent protein-C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross-presentation in CTL induction against OVA [257][258][259][260][261][262][263][264] epitope and in the antitumor efficacy induced by anti-CD137 mAb.Key words: CD137 (4-1BB) . Cross-priming . CTL . DC . Tumor immunity Supporting Information available online Introduction CD137, also known as 4-1BB, is a TNF-receptor family costimulatory molecule originally identified on activated T cells [1]. Its natural ligand CD137L is found on APC, including B cells, macrophages, and DC [2]. In the presence of TCR engagement, signaling through CD137 leads to increased T-cell proliferation, cytokine production, and prolonged CD8 1 T-cell survival in vitro [2]. Administration of agonistic anti-CD137 mAb either alone or following peptide vaccination is capable of inducing the eradication of established tumors in several transplantable tumor models [3,4]. This anti-tumor effect is dependent on CD8 1 T cells that show increases in tumor-specific cytotoxic activity and associated IFN-g production [3,4]. Recent studies have demonstrated that the activity of anti-CD137 mAb treatment is also dependent on their ability to enhance the survival of CD8 1 CTL, and on the prevention/reversal of established anergy [5][6][7]. In addition, antigen-independent anti-CD137 mAb effects have been described for memory T cells, and CD137 seems to be an Ã These authors contributed equally to this work.ÃÃ These authors share equal senior authorship. 2424important player in the differentiation of memory cells [8][9][10]. CD137 can also be expressed by activated NK cells [11], myeloid leukocytes [12] including DC [13,14], and tumor endothelial cells [15]. However, the role of CD137 molecules expressed on these non-T cells during tumor immunotherapy remains undefined [13,16].As naïve CTL do not express CD137 on their surface, susceptibility to CD137 triggering depends on prior up-regulation of this receptor [5]. This requires antigen rec...

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Section: Discussionmentioning

confidence: 99%

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confidence: 89%

In vivo depletion of DC impairs the anti‐tumor effect of agonistic anti‐CD137 mAb

et al. 2009

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“…Freshly isolated human PDCs are poor antigen-presenting cells, but upon activation by viruses, CpG, IL-3 and CD40L they acquire full DCs morphology and phenotype, presenting antigen to CD4+ T cells, and cross-priming of CD8+ T cells, albeit less efficiently than classical MDCs [17,[27][28][29]. The DCs features of PDCs in vitro are not demonstrated easily on tissue PDCs [1], possibly results from loss of specific PDCs markers (e.g.…”

Section: Background On Pdcs: History and Functionmentioning

confidence: 99%

Trafficking properties of plasmacytoid dendritic cells in health and disease

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et al. 2010

Trends in Immunology

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“…Although some studies show that pDCs phagocytose apoptotic cells (16,17), several report that pDCs hardly take up particulates, such as apoptotic cells (18), latex beads (17,19), zymosan granules (14), or extracellular bacteria (3). Human pDCs have been shown to prime functional T cell responses on phagocytosis of apoptotic debris (16). However, Piccioli and coworkers (3) postulate that pDCs cannot phagocytose bacteria (Staphylococcus aureus and Escherichia coli) and require myeloid DCs to respond to bacterial stimuli.…”

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confidence: 99%