Cross-priming versus cross-tolerance: are two signals enough?

doi:10.1016/S1471-4906(02)02185-3

Trends in Immunology

Volume 23, Issue 4, 1 April 2002, Pages 171-173

https://doi.org/10.1016/S1471-4906(02)02185-3 Get rights and content

Abstract

Depending on their state of maturation, dendritic cells (DCs) can cross-prime or cross-tolerize T cells. Mature DCs provide T-cell-receptor ligands (signal 1) and costimulatory molecules (signal 2), and activate T cells. Immature DCs provide signal 1, but not signal 2, and tolerize T cells. However, new data show that it is not the expression of costimulatory molecules alone that determines whether DCs induce immunity or tolerance, because mature DCs can induce tolerance also.

Section snippets

Immature DCs induce tolerance

During the negative selection of T cells in the thymus, not all self-antigens are presented. This allows self-reactive T cells to leave the thymus and requires additional mechanisms in the periphery to maintain self-tolerance, for which DCs might be responsible. Subtle differences in DC maturation might determine whether T-cell immunity is turned into tolerance 10., 11.. Under steady-state conditions (i.e. in the absence of infection or inflammatory stimuli), there appears to be a continuous

Mature DCs can induce tolerance also

The view that the maturation state of DCs determines whether T-cell cross-priming or cross-tolerance occurs was challenged recently [13]. Albert and colleagues isolated immature DCs by culturing peripheral-blood mononuclear cells with IL-4 and granulocytecolony-stimulating factor in vitro. These DCs were then matured by further culture with tumor necrosis factor α (TNF-α) and prostaglandin E₂ (PGE₂). The mature DCs tolerized cocultured human CD8⁺ T cells to cross-presented antigens from

Conclusion

The findings of Albert et al. raise the question of whether the distinction between immature and mature DCs based on their expression of costimulatory molecules is an oversimplification that does not account for the plasticity of DCs and the multiple types of T-cell response they can induce [20]. This diversity can be seen if in vitro-generated DCs are exposed to three different pathogens (Escherichia coli, Candida albicans and influenza virus) [21]. Each maturation stimulus induces a

Acknowledgements

We thank Thomas Kammertoens for helpful discussions. This work was supported by grants from the Deutsche Krebshilfe Mildred-Scheel-Stiftung e.V. (10-1535-BL2), Deutsche Forschungsgemeinschaft (SFB 506) and Bundesministerium für Bildung und Forschung (BMBF-01KV9911).

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Trends in Immunology

Research updateCross-priming versus cross-tolerance: are two signals enough?

Abstract

Section snippets

Immature DCs induce tolerance

Mature DCs can induce tolerance also

Conclusion

Acknowledgements

Immunol. Today

Immunobiology of dendritic cells

Annu. Rev. Immunol.

The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T-cell function

Nat. Immunol.

A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell

Nature

CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection

J. Virol.

Cross-presentation, dendritic cells, tolerance and immunity

Annu. Rev. Immunol.

Induction of a CD8+ cytotoxic T-lymphocyte response by cross-priming requires cognate CD4+ T-cell help

J. Exp. Med.

Immature dendritic cells acquire CD8+ cytotoxic T-lymphocyte priming capacity upon activation by T-helper-cell-independent or -dependent stimuli

J. Exp. Med.

Help for cytotoxic T-cell responses is mediated by CD40 signalling

Nature

T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions

Nature

The induction of tolerance by dendritic cells that have captured apoptotic cells

J. Exp. Med.

Research update
Cross-priming versus cross-tolerance: are two signals enough?

A conditioned dendritic cell can be a temporal bridge between a CD4⁺ T-helper and a T-killer cell

CD4⁺ T cells are required to sustain CD8⁺ cytotoxic T-cell responses during chronic viral infection

Induction of a CD8⁺ cytotoxic T-lymphocyte response by cross-priming requires cognate CD4⁺ T-cell help

Immature dendritic cells acquire CD8⁺ cytotoxic T-lymphocyte priming capacity upon activation by T-helper-cell-independent or -dependent stimuli