Unappreciated complexity in T cell help for dendritic cells

3 months ago 9

CD40 has long been known as a co-stimulatory molecule involved in T cell help for dendritic cells, and thereby as a contributor to CD8+ T cell immunity against cancers and infections. However, CD40 signaling drives complex functional responses that can contribute to tumor-specific CD8+ T cell responses in unexpected ways.

Wu et al. sorted CD40hi migratory cDC1s from skin-draining lymph nodes, stimulated these cells in vitro via CD40 and observed increased transcription of several genes, including those encoding CD70, 4-1BB, COX-2 and BCL-XL3. CD40 stimulation of bone-marrow-derived cDC1s combined with activation by polyinosinic:polycytidylic acid induced comparable gene expression patterns. To test the function of these molecules in the context of DC–CD8+ T cell interactions, the authors inoculated mice with immunogenic fibrosarcoma cells that can be rejected by helper-dependent CD8+ T cell responses4. Given the broad expression of some of these molecules, the authors also generated several new mouse lines in which CD70, 4-1BB, COX2 and BCL-XL were selectively missing from cDC1s and compared their response to wild-type mice and mice lacking CD40 specifically from cDC1s (Xcr1Cre × Cd40fl, referred to as CD40cKO).

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Fig. 1: Possible mechanisms mediating T cell help for cDC1 capacity priming.


  1. Ardouin, L. et al. Immunity 45, 305–318 (2016).

    Article  CAS  Google Scholar 

  2. Bedoui, S. et al. Immunol. Rev. 272, 52–64 (2016).

    Article  CAS  Google Scholar 

  3. Wu, R. et al. Nat. Immunol. https://doi.org/10.1038/s41590-022-01324-w (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ferris, S. T. et al. Nature 584, 624–629 (2020).

    Article  CAS  Google Scholar 

  5. Ahrends, T. et al. Immunity 47, 848–861 (2017).

    Article  CAS  Google Scholar 

  6. Bevan, M. J. Nat. Rev. Immunol. 4, 595–602 (2004).

    Article  CAS  Google Scholar 

  7. Roberts, E. W. et al. Cancer Cell 30, 324–336 (2016).

    Article  CAS  Google Scholar 

  8. Busselaar, J. et al. Front. Immunol. 11, 592569 (2020).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Microbiology and Immunology at the Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia

    Sammy Bedoui & Thomas Gebhardt

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Correspondence to Sammy Bedoui.

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The authors declare no competing interests.

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Bedoui, S., Gebhardt, T. Unappreciated complexity in T cell help for dendritic cells. Nat Immunol (2022). https://doi.org/10.1038/s41590-022-01335-7

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  • Published: 21 October 2022

  • DOI: https://doi.org/10.1038/s41590-022-01335-7

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