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Natural adjuvants: Endogenous activators of dendritic cells

Nature Medicine volume 5, pages 1249–1255 (1999)Cite this article

Abstract

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 stimulate a primary immune response, and they may represent the natural initiators of transplant rejection, spontaneous tumor rejection, and some forms of autoimmunity.

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Figure 1: Resting dendritic cells can be activated by mechanical manipulation in the absence of foreign substances.
Figure 2: Resting dendritic cells can be activated by co-culture with necrotic syngeneic cells.
Figure 3: Resting dendritic cells are able to engulf necrotic as well as apoptotic fibroblasts.
Figure 4: Functional activation of dendritic cells.
Figure 5: IFN-α activates dendritic cells.
Figure 6: Priming naive T cells.

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Acknowledgements

We thank A. Bendelac, L. D'Adamio, R.N. Germain and R.H. Schwartz for critically reading the manuscript, H. Arnheiter for an initial gift of IFN-α and advice, R. Caricchio for suggestions, O. Alpan for reading 'blind' the delayed-type hypersensitivity results, and members of the Ghost Lab (O. Alpan, C. Anderson, L. Bonney, S. Celli, A. Frank, B. Massey, J.P. Ridge, T. Kamala) and the Laboratory for Cellular and Molecular Immunology for the supportive environment. S.G. was partially supported by a fellowship from Universita' Cattolica del Sacro Cuore (Rome, Italy); and M.L., by a fellowship from the Dutch Government.

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  1. Ghost Lab, T cell Tolerance and Memory Section, Laboratory for Cellular and Molecular Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Stefania Gallucci, Martijn Lolkema & Polly Matzinger

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  1. Stefania Gallucci
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Correspondence to Stefania Gallucci.

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Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: Endogenous activators of dendritic cells. Nat Med 5, 1249–1255 (1999). https://doi.org/10.1038/15200

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