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Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function

Abstract

Dendritic cells (DCs) can be activated directly by triggering of receptors for pathogens or, indirectly, by exposure to inflammatory signals. It remains unclear, however, whether the two pathways result in qualitatively similar DCs or lead to equivalent adaptive immune responses. Here we report that indirect activation by inflammatory mediators generated DCs that supported CD4+ T cell clonal expansion but failed to direct T helper cell differentiation. In contrast, exposure to pathogen components resulted in fully activated DCs that promoted T helper responses. These results indicate that inflammation cannot substitute for contact with pathogen components in DC activation and suggest that the function of pattern recognition by DCs is to couple the quality of the adaptive immune response to the nature of the pathogen.

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Figure 1: Indirect DC activation by inflammatory signals in vitro.
Figure 2: Indirect DC activation by inflammatory signals in vivo.
Figure 3: Ex vivo T cell stimulatory capacity of directly versus indirectly activated DCs.
Figure 4: CD4+ T cells recognizing antigen on indirectly activated APCs clonally expand but do not become IFN-γ-producing effectors.
Figure 5: Indirectly activated APCs do not support the priming of helper T cells.

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Acknowledgements

We thank A. Eddaoudi for FACSorting services; C. Watkins for animal husbandry; K. Rowan for secretarial support; and M. Albert (Institut Pasteur, Paris, France), M. Bachmann (Cytos Biotechnology, Zürich, Switzerland), F. Batista (Cancer Research UK, London, UK), P. Matzinger (National Institutes of Health, Bethesda, Maryland), A. Oxenius (Swiss Federal Institute of Technology, Zürich, Switzerland) and members of the Immunobiology Laboratory, Cancer Research UK, for advice and critical review of the manuscript. Supported by Cancer Research UK.

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Correspondence to Caetano Reis e Sousa.

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Supplementary information

Supplementary Fig. 1

Similar in vivo division and expansion of T cells induced by directly versus indirectly activated APCs. (PDF 259 kb)

Supplementary Fig. 2

CD4+ T cells expanded by indirectly-activated APCs fail to develop into IFN-γ-producing effectors. (PDF 206 kb)

Supplementary Fig. 3

Use of flagellin as adjuvant allows induction of OVA-specific IgG1 in Myd88-sufficient mice. (PDF 121 kb)

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Spörri, R., Reis e Sousa, C. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol 6, 163–170 (2005). https://doi.org/10.1038/ni1162

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