Migratory Dendritic Cells Transfer Antigen to a Lymph Node-Resident Dendritic Cell Population for Efficient CTL Priming

Allan, Rhys S.; Waithman, Jason; Bedoui, Sammy; Jones, Claerwen M.; Villadangos, José A; Zhan, Yifan; Lew, Andrew M.; Shortman, Ken; Heath, William R.; Carbone, Federico

doi:10.1016/j.immuni.2006.04.017

Cited by 637 publications

(684 citation statements)

References 55 publications

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“…The former is generally considered a functional hallmark of DC, which are more motile than macrophages, and thus more commonly migrate to regional lymphoid tissue where they present processed antigen to the adaptive immune system (7,185). Macrophages, on the other hand, are less efficient at antigen presentation, but are well suited for phagocytic clearance of cellular debris due to their catabolic phenotype (117).…”

Section: The Mononuclear Phagocyte Systemmentioning

confidence: 99%

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

Hull

Agarwal

George

2014

Antioxidants & Redox Signaling

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Significance: Heme oxygenase-1 (HO-1) is a potential therapeutic target in many diseases, especially those mediated by oxidative stress and inflammation. HO-1 expression appears to regulate the homeostatic activity and distribution of mononuclear phagocytes ( MP) in lymphoid tissue under physiological conditions. It also regulates the ability of MP to modulate the inflammatory response to tissue injury. Recent Advances: The induction of HO-1 within MP-particularly macrophages and dendritic cells-modulates the effector functions that they acquire after activation. These effector functions include cytokine production, surface receptor expression, maturation state, and polarization toward a pro-or anti-inflammatory phenotype. The importance of HO-1 in MP is emphasized by their expression of specific receptors that primarily function to ingest heme-containing substrate and deliver it to HO-1. Critical Issues: MP are the first immunological responders to tissue damage. They critically affect the outcome of injury to many organ systems, yet few therapies are currently available to specifically target MP during disease pathogenesis. Elucidation of the role of HO-1 expression in MP may help to direct broadly applicable therapies to clinical use that are based on the immunomodulatory capabilities of HO-1. Future Directions: Unraveling the complexities of HO-1 expression specifically within MP will more completely define how HO-1 provides cytoprotection in vivo. The use of models in which HO-1 expression is specifically modulated in bone marrow-derived cells will allow for a more complete characterization of its immunoregulatory properties.

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Section: The Mononuclear Phagocyte Systemmentioning

confidence: 99%

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

Hull

Agarwal

George

2014

Antioxidants & Redox Signaling

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“…Those results imply the potential roles of exosomes in immune privileges in the placenta. Tumor-specific exosomes are also found in the blood of tumor patients and their levels increase as the tumor-burden of patients increases (Allan et al, 2006;Almqvist et al, 2008;Bullerdiek and Flor, 2012;Huber et al, 2008;Karlsson et al, 2001).…”

Section: Generation Of Exosomes In Vivomentioning

confidence: 99%

“…Some data have shown that DCs release exosomes in vivo (Allan et al, 2006). Antigen-sharing between different types of DCs is easily observed in mouse experimental models, and this antigen sharing is thought to take place via exosomes.…”

Section: Generation Of Exosomes In Vivomentioning

confidence: 99%

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

Hwang

2013

Molecules and Cells

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The host immune response involves a variety of cell types, including specialized immune and non-immune cells. The delicate coordination among these cells via close communication is central for the proper operation of immune system. Cell-cell communication is mediated by a complex network that includes soluble factors such as cytokines, chemokines, and metabolites exported from cells, as well as membrane-bound receptors and their ligands. Cell-cell communication is also mediated by membrane vesicles (e.g., exosomes, ectosomes), which are either shed by distant cells or exchanged by cells that are making direct contact. Intercellular communication via extracellular membrane vesicles has drawn much attention recently, as they have been shown to carry various biomolecules that modulate the activities of recipient cells. In this review, I will discuss current views on cell-cell communication via extra-cellular membrane vesicles, especially shedded membrane vesicles, and their effects on the control of the immune system.

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“…However, maturation of CD8␣ DCs indicates that perhaps cDCs are migrating to the draining MLN and transferring the Ags to CD8␣ DCs, which results in maturation of CD8␣ DCs. Mature CD8␣ DCs may then go on to induce CD8 ϩ T cell response, as has been observed with lung and s.c. infection using HSV (28,29). Moreover, CD103 ϩ DCs with the ability to cross-present inhaled Ags and migrate to draining MLN have also been identified in the mouse lung (30).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery

Kushwah

Cao

2008

The Journal of Immunology

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In spite of the extensive research in the field of gene therapy, host immune responses continue to be the major barrier in translating basic research to clinical practice. Helper-dependent adenoviral (HD-Ad) vectors show great potential for pulmonary gene therapy, but the knowledge of pulmonary immune responses toward these vectors is very limited. In this study, we show that HD-Ad vectors are potent stimulators of dendritic cell (DC) maturation, thus leading to stimulation of T cell proliferation with ∼6% of naive CD4+ T cells from pulmonary mediastinal lymph node responding to HD-Ad-treated DCs. In contrast to the belief that HD-Ad vectors are unable to prime adaptive immune response, we show for the first time, through in vivo pulmonary studies in mice, that HD-Ad vectors can prime CD4+ and CD8+ T cell responses in the lung at high and substantially low doses. This indicates cross-presentation of HD-Ad-derived epitopes by DCs to prime CD8+ T cell responses. To assess the basis of pulmonary T cell response against HD-Ad vectors, we examined the response of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the lung. In response to HD-Ad delivery, there is induction of maturation in both cDC and pDC subsets, but it is the cDCs, not pDCs, that migrate rapidly to draining lymph nodes within the first 2 days after vector delivery to prime adaptive immune response against these vectors. These findings have implications for development of strategies to prevent adaptive immune responses against gene therapy vectors.

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Migratory Dendritic Cells Transfer Antigen to a Lymph Node-Resident Dendritic Cell Population for Efficient CTL Priming

Cited by 637 publications

References 55 publications

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery

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