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.

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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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