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Minimal activation of memory CD8+ T cell by tissue-derived dendritic cells favors the stimulation of naive CD8+ T cells

Nature Immunology volume 8, pages 1060–1066 (2007)Cite this article

Abstract

Of the many dendritic cell (DC) subsets, DCs expressing the monomorphic coreceptor CD8 α-chain (CD8α) are localized permanently in lymphoid organs, whereas 'tissue-derived DCs' remain in nonlymphoid tissues until they 'capture' antigen and then move to local lymph nodes. Here we show that after lung infection, both naive and memory CD8+ 'killer' T cells responded to influenza virus antigens presented by lymph node–resident CD8α+ DCs, but only naive cells responded to antigens presented by lung-derived DCs. This difference provides a mechanism for priming naive T cell responses in conditions in which robust memory predominates. Our findings have implications for immunity to pathogens that can mutate their T cell epitopes, such as influenza virus and human immunodeficiency virus, and challenge the long-held view that memory T cells have less-stringent requirements for activation than naive T cells have.

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Figure 1: Naive but not memory CD8+ T cells proliferate in response to lung-derived DCs from the mediastinal lymph nodes of mice infected with influenza virus.
Figure 2: Prolonged antigen presentation by lung-derived DCs allows in vivo population expansion of naive but not memory antigen-specific CD8+ T cells late in infection.
Figure 3: Capacity of DC subtypes to stimulate naive and memory CD8+ T cells.
Figure 4: Competition between naive and memory T cells in vivo.

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Acknowledgements

We thank J. Langley, M. Camilleri and the WEHI Flow Cytometry Facility for technical assistance; and J. Miller for discussions. Supported by the National Health and Medical Research Council (Australia), the Wellcome Trust (G.T.B.), the Howard Hughes Medical Institute (G.T.B. and W.R.H.) and the Deutsche Forschungsgemeinschaft (BE 3285/1-1 and BE 3285/1-2 to S.B.).

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Authors and Affiliations

  1. Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, 3050, Victoria, Australia

    Gabrielle T Belz, Sammy Bedoui, Fiona Kupresanin & William R Heath

  2. Department of Microbiology and Immunology, The University of Melbourne, Melbourne, 3010, Victoria, Australia

    Francis R Carbone

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  1. Gabrielle T Belz
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  2. Sammy Bedoui
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Correspondence to Gabrielle T Belz or William R Heath.

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Belz, G., Bedoui, S., Kupresanin, F. et al. Minimal activation of memory CD8+ T cell by tissue-derived dendritic cells favors the stimulation of naive CD8+ T cells. Nat Immunol 8, 1060–1066 (2007). https://doi.org/10.1038/ni1505

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