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Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8+ T cell responses to influenza

An Erratum to this article was published on 01 July 2010

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Abstract

The question of which dendritic cells (DCs) respond to pulmonary antigens and cross-prime CD8+ T cells remains controversial. We show here that influenza-specific CD8+ T cell priming was controlled by different DCs at different times after infection. Whereas early priming was controlled by both CD103+CD11blo and CD103CD11bhi DCs, CD103CD11bhi DCs dominated antigen presentation at the peak of infection. Moreover, CD103CD11bhi DCs captured exogenous antigens in the lungs and directly cross-primed CD8+ T cells in the draining lymph nodes without transferring antigen to CD8α+ DCs. Finally, we show that CD103CD11bhi DCs were the only DCs to express CD70 after influenza infection and that CD70 expression on CD103CD11bhi DCs licensed them to expand CD8+ T cell populations responding to both influenza and exogenous ovalbumin.

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Figure 1: NP-specific CD8+ T cells in the mLNs precede those in the lungs.
Figure 2: DC subsets in mLN after influenza infection.
Figure 3: Influenza infection triggers the recruitment of CD103CD11bhi tDCs to the mLNs.
Figure 4: CD103CD11bhi tDCs accumulate in the lungs after influenza infection.
Figure 5: CD103CD11bhi tDCs continue to present antigen at late times after infection.
Figure 6: CD103CD11bhi tDCs cross-present soluble antigens captured in the lungs.
Figure 7: CD70 expression is a hallmark of CD103CD11bhi tDCs.
Figure 8: CD70 expression on CD103CD11bhi tDCs promotes the population expansion of NP-specific CD8+ T cells.

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Change history

  • 07 May 2010

    In the version of this article initially published, the label along the vertical axis of Figure 6h was incorrect. The correct label is “OT-II proliferating cells (×102).” The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank L. LaMere and K. Martin for animal husbandry, and the members of the University of Rochester Medical Center Flow Cytometry Core Facility for cell sorting. Supported by the University of Rochester and the National Institutes of Health (AI61511 and HL69409 to T.D.R., and AI06856 to F.E.L.).

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Contributions

A.B.-T. designed and did the experiments, analyzed the data and wrote the paper; B.L. optimized the DC-subsetting protocol and helped interpret the data; F.E.L. helped supervise the project and edit the paper and T.D.R. supervised the project, helped design the experiments and edited the paper.

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Correspondence to Troy D Randall.

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The authors declare no competing financial interests.

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Ballesteros-Tato, A., León, B., Lund, F. et al. Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8+ T cell responses to influenza. Nat Immunol 11, 216–224 (2010). https://doi.org/10.1038/ni.1838

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