Natural adjuvants: Endogenous activators of dendritic cells

  title={Natural adjuvants: Endogenous activators of dendritic cells},
  author={Stefania Gallucci and Martijn P. Lolkema and Polly Matzinger},
  journal={Nature Medicine},
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… 

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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.

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Current issues in dendritic cell cancer immunotherapy.

  • J. LópezD. Hart
  • Biology, Medicine
    Current opinion in molecular therapeutics
  • 2002
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

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.



Dendritic cells and the control of immunity

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.

The dendritic cell system and its role in immunogenicity.

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

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?

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.

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

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.

Human CD14 mediates recognition and phagocytosis of apoptotic cells

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

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.