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Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance

Open access
Steinman, Ralph Marvin, Nussenzweig, Michel C.·2002·Proceedings of the National Academy of Sciences

Abstract

The immune system generally avoids horror autotoxicus or autoimmunity, an attack against the body's own constituents. This avoidance requires that self-reactive T cells be actively silenced or tolerized. We propose that dendritic cells (DCs) play a critical role in establishing tolerance, especially in the periphery, after functioning T cells have been produced in the thymus. In the steady state, meaning in the absence of acute infection and inflammation, DCs are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. Nevertheless, immature DCs continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature DCs silence T cells either by deleting them or by expanding regulatory T cells. This capacity of DCs to induce peripheral tolerance can work in two opposing ways in the context of infection. In acute infection, a beneficial effect should occur. The immune system would overcome the risk of developing autoimmunity and chronic inflammation if, before infection, tolerance were induced to innocuous environmental proteins as well as self antigens captured from dying infected cells. For chronic or persistent pathogens, a second but dire potential could take place. Continuous presentation of a pathogen by immature DCs, HIV-1 for example, may lead to tolerance and active evasion of protective immunity. The function of DCs in defining immunologic self provides a new focus for the study of autoimmunity and chronic immune-based diseases.

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Metadata

Authors
Steinman, R. M., & Nussenzweig, M. C.
Venue
Proceedings of the National Academy of Sciences
Published
2002-01-02
Volume
99
Issue
1
Pages
351-358
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1997708871
Cited by
1,166
References
9
FWCI
37.42
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance. https://app.cochat.ai/papers/10.1073/pnas.231606698
The paper
Steinman, R. M., & Nussenzweig, M. C. (2002). Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.231606698

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.