Natural adjuvants: Endogenous activators of dendritic cells

@article{Gallucci1999NaturalAE,
  title={Natural adjuvants: Endogenous activators of dendritic cells},
  author={Stefania Gallucci and Martijn P Lolkema and Polly Matzinger},
  journal={Nature Medicine},
  year={1999},
  volume={5},
  pages={1249-1255}
}
Dendritic cells, the most potent antigen-presenting cells, need to be activated before they can function to initiate an immune response. We report here that, in the absence of any foreign substances, dendritic cells can be activated by endogenous signals received from cells that are stressed, virally infected or killed necrotically, but not by healthy cells or those dying apoptotically. Injected in vivo with an antigen, the endogenous activating substances can function as natural adjuvants to… 

Figures and Topics from this paper

Dendritic cells resurrect antigens from dead cells.
TLDR
The role of dendritic cells are discussed in stimulating MHC class I-restricted T-cell responses by exogenous routes, which can induce CD8(+) CTLs by phagocytosis of dead tumor or virus-infected cells.
Dendritic cells signal T cells in the absence of exogenous antigen
TLDR
It is found that DC-mediated activation results in antigen-independent cytokine gene expression, which points to a new role for DCs in shaping the cytokine milieu.
The cell biology of antigen presentation in dendritic cells.
Dendritic cells are the most efficient antigen-presenting cells. They take up antigens and pathogens, generate MHC-peptide complexes, migrate from the sites of antigen acquisition to secondary
Tumour escape from immune surveillance through dendritic cell inactivation.
TLDR
The current knowledge of the physiopathology of DC in cancer is reviewed, which paves the way for novel strategies of therapeutic intervention.
Activation of dendritic cells: translating innate into adaptive immunity.
TLDR
Understanding which of these signs are both necessary and sufficient to convert DCs into the immunostimulatory antigen-presenting cells that prime appropriate effector T cells may hold the key to improved strategies for vaccination and immunotherapy.
Activation of dendritic cells: translating innate into adaptive immunity.
TLDR
Understanding which of these signs are both necessary and sufficient to convert DCs into the immunostimulatory antigen-presenting cells that prime appropriate effector T cells may hold the key to improved strategies for vaccination and immunotherapy.
Novel activators of dendritic cells as fundamental tools in immunotherapy
TLDR
A better characterisation of the currently known dendritic cell activators, and the discovery of new ones, will lead to safer and more efficacious vaccines.
Current issues in dendritic cell cancer immunotherapy.
Dendritic cells (DCs) initiate and direct the immune response. Their inability to detect danger signals from transformed cells and to generate an effective immunological response may allow cells with
HMGB1 is an endogenous immune adjuvant released by necrotic cells
TLDR
In vivo, HMGB1 enhances the primary antibody responses to soluble antigens and transforms poorly immunogenic apoptotic lymphoma cells into efficient vaccines and reduces the activation induced by necrotic wild‐type cell supernatants.
The modulation of immunity by dendritic cells
TLDR
Antigen-pulsed DCs have been used to induce anti-tumor T cell and clinical responses in humans, apparently without significant toxicity and may be valuable tools for modulating immunity in the setting of autoimmunity, cancer, and chronic viral infections.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 55 REFERENCES
Dendritic cells and the control of immunity
TLDR
Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis and the realization that these cells are a powerful tool for manipulating the immune system is realized.
Origin, maturation and antigen presenting function of dendritic cells.
TLDR
Dendritic cells represent the natural adjuvants for T cell responses and their therapeutic exploitation in the near future is foreseen.
The dendritic cell system and its role in immunogenicity.
  • R. Steinman
  • Biology, Medicine
    Annual review of immunology
  • 1991
TLDR
Dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells.
Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs
TLDR
It is shown that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs, suggesting a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of C TLs.
Can B cells turn on virgin T cells?
TLDR
The presenting capacity of B cells in vivo is examined and it is found that resting B cells are indeed unable to activate resting T cells.
Immunogenicity of apoptotic cells in vivo: role of antigen load, antigen-presenting cells, and cytokines.
TLDR
It is shown that injection of apoptotic RMA cells, a syngeneic T cell lymphoma, into C57BL/6 mice results in priming of a functional and long-lasting tumor-specific immune response, and the different roles of Mphi and DCs in the physiologic clearance of unwanted cells are outlined and have implications in designing immunomodulating vaccines.
Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1
TLDR
TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly.
Innate Immunity: The Virtues of a Nonclonal System of Recognition
TLDR
Characterization of the nonclonal receptors of the innate immune system responsible for the adjuvant activity, and, evidently, for the associated side effects, would provide a powerful alternative approach, which would ultimately allow one to target these receptors directly.
Human CD14 mediates recognition and phagocytosis of apoptotic cells
TLDR
Results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with ‘non-self’ components (LPS) and ‘self” components (apoptotic cells) produce distinct macrophage responses.
Immunosuppressive effects of apoptotic cells
TLDR
The presence of apoptotic cells during monocyte activation increases their secretion of the anti-inflammatory and immunoregulatory cytokine interleukin 10 (IL-10) and decreases secretion ofthe proinflammatory cytokines tumour necrosis factor-α (TNF-α), IL-1 and IL-12, which may inhibit inflammation and contribute to impaired cell-mediated immunity in conditions associated with increased apoptosis.
...
1
2
3
4
5
...